1st semester

IMMUNOLOGY AND SEROLOGY PRELIMS CALAMBA DOCTORS’ COLLEGE AY 2022 - 23

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RODRIGUEZ, PATRICIA JEAN J.
BSMT3-B
Immunology & Serology-2022
OUTLINE
I. Definition of terms.
II.HISTORICAL DEVELOPMENT
III. Immunity
A. Types of Immunity
B. Cellular components of Immunity
C. Humoral Component of natural immunity
III. Cellular Defeense
A. SUBTOPIC
Definition of terms.
Acquired Immunodeficiency Syndrome- A life threatening disease
caused by a virus & characterized by breakdown of body’s
immune system
Agammaglobulinemia- An almost total lack of immunoglobulins,
or antibodies.
Allergen- any substance that causes allergy
Allergy- An inappropriate & harmful response of the body’s
immune system to normally harmless substance.
Anaphylactic shock- A life-threatening allergic reaction
characterized by swelling of body tissues including the
throat, difficulty in breathing, and sudden fall in blood
pressure.
Antibody- A soluble protein molecule produced and secreted by
B-cells in response to an antigen which is capable of binding
to that specific antigen.
Antigen- any substance that, when introduced to the body, is
recognized by the immune system.
Antigen-presenting cells- B-cells, cells of the monocyte lineage
(including macrophages and dendritic cells), and various
other body cells that “present” antigen in a form that T cells
can recognize.
Antinuclear antibody (ANA)- An autoantibody directed against a
substance in the cell’s nucleus.
Antiserum- Serum that contains antibodies
Antitoxins- antibodies that interlock with, and inactive toxins
produce by certain bacteria
Appendix- Lymphoid organ in the intestine
Attenuated- Weakened; no longer infectious
Autoantibody- An antibody that reacts against person’s own
tissue
Autoimmune disease- A disease that results when the immune
system mistakenly attacks the body’s own tissue.
Rheumatoid arthritis and systemic lupus er0079thematosus
are autoimmune disease
Basophil- a white blood cell that contributes to inflammatory
reactions. Along with mast cells, basophil is responsible for
the symptoms of allergy
B cells- Small white cells crucial to the immune defense. Also
known as B lymphocytes, they are derived from bone
marrow and develop into plasma cells that are the source of
antibodies.
Bone marrow- soft tissue located in cavities of the bones. The
bone marrow the source of all blood cells
Chromosomes- Physical structures in the cell’s nucleus that the
genes. Each human cell has 23 pair to chromosomes
Complement- A complex series of blood proteins whose action
“complements” the work of antibodies. Complement
destroys bacteria, produce inflammation, and regulates
immune reactions.
Complement cascade- A precise sequence of events usually
triggered by an antigen-antibody complex, in which each
component of the complement system is activated in turn.
Constant region- That part of an antibody’s structure that is
characteristic for each antibody class.
Co-Stimulation- The delivery of a second signal from an antigen-
presenting cell to a T cell. The second signal rescues the
activated T cell from anergy, allowing it to produce the
lymphokines necessary for the growth of additional T cells.
Cytokine- Powerful chemical substances secreted by cells.
Cytokines include lymphokines produced by lymphocytes
and monokines produced by monocytes and macrophages
Cytotoxins T cells- A subset of T lymphocytes that can kill body
cells infected by viruses or transformed by cancer
Dendritic cells- White blood cells found in the spleen and other
lymphoid organs. Dendritic cells typically use threadlike
tentacles to enmesh antigen, which they present to T cells.
DNA (deoxyribonucleic acid)- Nucleic acid that is found in the cell
nucleus and that is the carrier of genetic information
Enzyme- A protein produced by living cells, which promotes the
chemical process of life without itself being altered.
Eosinophil- A white blood cell that contains granules filled with
chemical damaging to parasites, and enzymes that damp
down inflammatory reactions
Epitone- A unique shape or maker carried on an antigen’s surface,
which triggers a corresponding antibody response.
Graft-versus-host disease (GVHD)- A life-threatening reaction in
which transplanted immunocompetent cells attack the
tissues of the recipient.
Granulocytes- White blood cells filled with granules containing
potent chemicals that allow the cells to digest

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IMMUNOLOGY AND SEROLOGY PRELIMS
microorganisms, or to produce inflammatory reactions.
Neutrophils, eosinophil, and basophils are examples of
granulocytes.
Helper T cells- A subset to T cells that typically carry the T4
marker and are essential for turning on antibody
production, activating cytotoxin T cells, and initiating many
other immune responses
Hematopoiesis- The information and development of blood cells,
usually takes place in the bone marrow
Histocompatibility testing- A method of matching the self-
antigens (HLA) on the tissue of a transplant donor with
those of the recipient. The closer the match, the better the
chance that the transplant will take
HIV (human immunodeficiency virus)- The virus that causes AIDS
Human leukocyte antigens (HLA)-Protein in markers of self-used
histocompatibility testing. Some HLA types also correLate
with certain autoimmune diseases
Hybridoma- A hybrid cells created by fusing a B lymphocyte with a
long-lived neoplastic plasma cell, or a T lymphocyte with a
lymphoma cell. A B-cell hybridoma secretes a single specific
antibody.
Hypogammaglobulinemia- Abnormally low levels of
immunoglobulins.
Idiotypes-The unique and characteristics parts of an antibody’s
variable region, which can themselves serve as antigens.
Immune complex- A clusters of interlocking antigens and
antibodies
Immunoassay- A test using antibodies to identify and the quantify
substances. Often the antibody is linked to marker such as a
fluorescent molecule, a radioactive molecule, or an enzyme
Immunocompetent- Capable of developing an immune response
Immunoglobulins- A family of large protein molecules, also
known as antibodies.
Immunosuppression- reduction of the immune responses, for
instance by giving drugs to prevent transplant rejection
Immunotoxin- A monoclonal antibody linked to a natural toxin, a
toxin drug, or a radioactive substance
Inflammatory response- Redness, warmth, swelling, pain, and
loss of function produce in response to infection, as the
result of increased flood flow and an influx of immune cells
and secretions.
Interleukins- A major group of lymphokines and monokines.
Langerhans cells- Dendritic cells in the skin that pick-up antigen
and transport it to lymph node
Leukocytes- all white blood cells
Lymph- a transparent, slightly yellow fluid that carries
lymphocytes, bathes the body tissue, and drains into the
lymphatic vessels
Lymphatic vessels- A bodywide network of channels, similar to
the blood vessels, which transport lymph to the immune
organs and into the bloodstream
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CALAMBA DOCTORS’ COLLEGE AY 2022 - 23
Lymph nodes- small bean-shaped organs of the immune system,
distributed widely throughout the body and the linked by
lymphatic vessels. Lymph nodes are garrisons of B, T, and
other immune cells
Lymphocytes- Small white blood cells produced in the lymphoid
organ’s paramount in the immune defense
Lymphoid organs- The organs of the immune system, where
lymphocytes develop and congregate. They include the
bone marrow, thymus nodes, spleen, and various other
cluster of lymphoid tissue, the blood vessel and lymphatic
vessels can also be considered lymphoid organs
Lymphokines- Powerful chemicals substances secreted by
lymphocytes. These soluble molecules help direct and
regulate the immune responses
Macrophage- A larger and versatile immune cell that acts as a
microbe-devouring phagocyte, an antigen-presenting cell,
and an important source of immune secretions; cell eating.
Major histocompatibility complex (MHC)- A group of genes that
controls several aspects of the immune response. MHC
genes code for self-markers on all body cell
Mast cell- A granule-containing cell found in tissue. The contents
of mast cells, along with those of basophils, are responsible
for the symptoms of allergy.
Monoclonal antibodies- Antibodies produced by a single cell or its
identical progeny, specific for a given antigen. as a tool for
binding to specific protein molecules, monoclonal
antibodies are invaluable in research, medicine, and
industry.
Monocyte- a large phagocytic white blood cell that, when it
enters tissue, develops into a macrophage
Monokines- Powerful chemical substance secreted by monocytes
and macrophages. These soluble molecules help direct and
regulate the immune responses.
Natural killer (NK) cells- large granule-filled lymphocytes that take
on tumor’s cells and infected body cells. They are known as
“natural” killers because they attack without first having to
recognize specific antigens
Neutrophil- A white blood cell that is an abundant and important
phagocyte
Nucleic acids- Large, naturally occurring molecules composed of
chemical blocks known as nucleotides. There are two kinds
of nucleic acids, DNA and RNA
OKT3- A monoclonal antibody that targets mature T cells
Opsonize- To coat an organism with antibodies or a complement
protein so to make it palatable to phagocytes
Organism- An individual living thing
Peyer’s patches- A collection of lymphoid tissues in the intestinal
tract
Phagocytes- large white blood cells that contribute to the
immune defenses by ingesting microbes or other cells and
foreign particles
Plasma cells- large antibody-producing cells that develop from B
cells
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Platelets- Granule-containing cellular fragments critical for blood Vaccine- A substance that contains antigenic components from an
clotting and sealing of wounds. Platelets also contribute to infectious organism. By simulating an immune response (but
the immune response not disease), it protects against subsequent infection by that
organism
Polymorphs- short for polymorphonuclear leukocytes or
granulocytes
Proteins- Organic compounds made up of amino acid. Protein are
one of the major constituents
Protozoa- A group of one-celled animals, a few of which cause
human disease (including malaria and sleeping sickness)
Rheumatoid Factor- An autoantibody found in the serum of most
persons with rheumatoid arthritis
RNA (ribonucleic acid)- A nucleic acid that is found in the
cytoplasm and also in the nucleus of some cells. One
function of RNA is to direct the synthesis of proteins
Serum- The clear liquid that separates from the blood when it is
allowed to clot. This fluid retains any antibodies that were
present in the whole blood
Severe combined immunodeficiency disease (SCID)- A life-
threatening condition in which infants are born lacking
major immune defense
Spleen- A lymphoid organ in the abdominal cavity that is an
important center for system activities.
Stem cells- cells from which all blood cells derive. The bone
marrow is rich in stem cells.
Subunit vaccine- a vaccine that uses merely one component of an
infectious agent, rather than the whole to simulate an
immune response
Super antigen- a class of antigens, including certain bacterial
toxins, which unleash a massive and damaging immune
response.
Suppressor T cells- A subset of T cells that turn off antibody
production and other immune responses
T cells- Small white blood cells that orchestrate and/or directly
participate in the immune defenses. Also known as T
lymphocytes, they are processed in the thymus and secrete
lymphokines
Thymus- A ordinary lymphoid organ, high in the chest, where T
lymphocytes proliferate and mature
TIL- Tumor-infiltrating lymphocytes. These immune cells are
extracted from the tumor tissue, treated in laboratory, and
reinjected into the cancer patient
Tissue typing- See histocompatibility testing
Tolerance- A state of nonresponsiveness to a particular antigen or
group of antigens
Topsis and adenoids- Prominent oval masses of lymphoid tissue
on either side of the throat
Toxins- Agent produced by plants and bacteria, normally very
damaging to mammalian cells, which can be delivered
directly to target cells by linking them to monoclonal
antibodies or lymphokines

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HISTORICAL DEVELOPMENT
Immunology
● Study of the reactions of a host when foreign substance is introduced to the body
● Study of all aspects of body defenses, such as antigens and antibodies, allergy & hypersensitivity
NOBEL PRIZE WINNERS IN IMMUNOLOGY (Turgeon)

YEAR SCIENTIST RESEARCH

1901 Emil Behring Serum antitoxins

1905 Robert Koch Cellular immunity in TB

1908 Elie Metchnikoff Phagocytosis

Paul Ehrlich Immunity

1913 Charles Richet Anaphylaxis

1919 Jules Bordet Complement

1930 Karl Landsteiner Human blood group antigens

1960 Macfarlane Burnet, Peter Medawar Discovery of immunologic tolerance

1972 Gerald Edelman, Rodney Porter Structure of antibodies

1977 Rosalyn Yalow Radioimmunoassay

1980 George Snell, Jean Dausset, Baruj Benaceraf Major histocompatibility complex

1984 Niels Jernem Immunoregulation

Georges Koehler, Cesar Milstein Monoclonal antibody

1987 Susumu Tonegawa Antibody diversity

1991 Edward Donnall Thomas, Joshep Murray Transplantation

1996 Peter Doherty, Rolf Zinkernagel Cytotoxic T cell recognition of virally

infected cells

2008 Francoise Barre-Sinoussi, Luc Montagnier Human immunodeficiency virus

Date Scientist(s) Discovery

1798 Jenner Smallpox vaccination

1862 Haeckel Phagocytosis

1880-1881 Pasteur Live, attenuated chicken cholera and

anthrax vaccine

1883-1905 Metchnikoff Cellular theory of immunity propoaad

1885 Pasteur Therapeutic vaccination First report of liva

“attenuated” vaccine for rabies

1890 Von Bahring Kiatasata Humoral theory of immunity proposed

1891 Koch Demonstration of cutaneous

(Delayed type) hypersensitivity

1900 Ehrlich Antibody formation theory

1902 Portier, Richet Immediate-hypersensitivity anaphylaxis

1903 Arthus Arthus reaction of intermediate

hypersensitivity
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1938 Marrack Hypothesis of antigen-antibody binding

1944 Hypothesis of allograft rejection

1949 Salk, Sabin Development of polio vaccines

1951 Reed Vaccine against yellow fever

1953 Graft-versus-host reaction

1957 Burnet Clonel selection theory

1957 Interferon

1958-1962 Human leukocyte antigens (HLAs)

1964-1968 T-cell and B-cell cooperation in immune

response

1972 Identification of antibody molecule

1975 Köhler First monoclonal antibodies

1985-1987 Identification of genes for T-cell receptor

1986 Monoclonal hepatitis B vaccine

1986 Mosmann Th1 versus Th2 model of T helper call

function

1996-1998 Identification of toll-like receptors

2001 FOXP3, the gene directing regulatory T cell

development

2005 Frazer Development of human papillomavirus

vaccine

Historical Perspectives (Stanley)

1798 Edward Jenner, an English countryside physician demonstrated that protection from cowpox could be
generated by the transfer of postural material from cowpox lesion instead of the more hazardous
smallpox lesion

1880 Louis Pasteur demonstrated that injection of killed microbes provided protection upon subsequent exposure to
live counterpart

1888 Eli Metchnikoff demonstrated that certain blood cells ingest foreign material

1894 Jules Bordet discovered complement

1897 Robert Kaus discovered precipitins

1901 Emil von Behring had the distinction of being awarded as the first immunology-related Nobel Prize for his works
on serum therapy

1984 Discovery of the T cell receptor gene

1987 Susumu Tonegawa was awarded the Nobel Prize for his discovery of the genetic principles underlying the
generation of antibodies with different specificities.
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lOMoARcPSD|163065INTRODUCTION ZG- DATE SCIENTISTS DISCOVERY

1798 Jenner Smallpox
vaccination
1862 Haekel phagocytosis
1880-1881 Pasteur Live, attenuated
Immunology chicken cholera
and anthrax vaccine
- study of a host’s reactions when foreign substances are introduced
1883-1905 Metchnikof Cellular theory
into the body
of immunity through
- as a science has its roots in the study of immunity, the condition of
being resistant to infection phagocytosis
1885 Pasteur Therapeutic
Antigen vaccination
- foreign substance that induces such as an immune response 1890 Von Behring, Proposed
Kitasata Humoral theory
- all Immunogen are antigen but not all antigens are Immunogen
of Immunity
Immunogen – are antigen, macromolecules capable of triggering adaptive 1891 Robert Koch Delayed type
immune response by inducing the formation of antibodies Immunity
Immunity – condition of being resistant to infection 1500’s 1900 Ehrlich Antibody
formation
• Chinese developed a practice of inhaling powder made from theory
smallpox scabs (langib) in order to produce protection against this 1902 Portier, Richet Immediate-
dreaded disease hypersensitivity
• Variolation – exposing an individual to materials from smallpox
lesion
1700’s

• Edward Jenner discovered a relationship between exposure to

cowpox and immunity to smallpox • All those physiological mechanisms that endow the animal with the
• Vaccination – injecting cellular material capacity to recognize materials as foreign to itself and to neutralize,
eliminate or metabolize them with or without injury to its own
• Vacca – Latin word for “cow”
tissues.
Cross-immunity • In normal circumstances, we tend to have immune response against
foreign
- which exposure to one agent produces protection against another
agent • Autoimmunity – autoimmune disease = abnormal
- • The immune system is structured to recognize, respond to, and
destroy a wide variety of invading organism that would otherwise
• AAAI - artificially acquired active immunity
be capable of promoting infections, harmful to the body.
• Old culture – can trigger immune response but not capable progress
host to disease state TYPES OF IMMUNITY
• Attenuated, inactivated, and toxoid – type of virus
Natural Immunity or Innate Immunity
1. Attenuated vaccine – not applicable in immunocompromised,
low immune system because pathogen is alive • ability of an individual to resist infections by means of normally
2. Inactivated vaccine – produced by killing the organism but present body functions.
capable (typhoid vaccine) • Non-specific
3. Toxoid vaccine – no longer toxin but immunogenic and can be • Naturally occurring at birth
used as vaccine • Lack of memory
(Diphtheria toxoid vaccine) • It has standardized response to all antigen Ex:
1885 - Skin, acidity of stomach, PMN, macrophage, phagocytic cells, NK
cells
• Pasteur tried out his new procedure to the boy who was bitten
• The boy received 12 injections and miraculously the boy survived
 has diverse response in each antigen

NATURAL IMMUNITY
External Defense System

• composed of structural barriers that prevent most infectious agents

from entering the body
• “First line of defense” Example:
-linings of the respiratory tract
- skin and mucosal membrane surfaces
- secretions
Sweat glands – IMMUNITYlactic acid
Sebaceous glands – fatty acids
Acidity of the stomach
-HCl produced by parietal cells
-pH 1-3
-ex: H. pylori (gastric ulcer) can resist urease enzyme
Tears and saliva – lysozyme
Internal Defense System

• Designed to recognize molecules that are unique to infectious

organism
• “Second line of disease”
■ Phagocytosis
• Most important function in the internal
Defense System
-engulfment of cells or particulate matter by
neutrophils (PMNs), macrophages and other cells

■ Inflammation of fever
■ Natural anti-microbial substances
• Complement pathway –
especially antibody dependent
pathways
Properdin
• Interferon
• TNF
• Beta-lysin

CELLULAR COMPONENTS OF NATURAL

■ Phagocytes
■ Other WBC’(granulocytes)
■ NK cells
- Kills viruses and tumor cells prior to exposure
- Lymphocytes
■ LAK cells
- NK – part of natural immunity - Effective in killing virus
- Kills cancer/tumor cells
Acquired Immunity or Adaptive Immunity - It has been shown that lymphocytes, when exposed to Iterleukin-2,
• type of resistance that is characterized by specificity for each are capable of lysing fresh, non-cultured cancer cells, both primary
individual pathogen, or and metastatic
microbial agent - The only problem when LAK cells use
• specific - Higher interleukin-2 can have side effect such as severe fluid
• not presence at birth retention
• it has memory B-cells HUMORAL COMPNENT OF NATURAL IMMUNITY
1. primary response - Compound substances
- first encounter the antigen/Immunogen • Cytokines
- wherein the body meets the antigen the first time around 2. • Complement pathway
secondary response
• Lysozymes
- already meet 1st, 2nd and so on
• Anti-microbial substances
- better than primary response • Beta-lysin
- immune response is fast than primary response
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CELLULAR DEFENSE MECHANISM • Possess grayish-blue cytoplasm and is groundglass in appearance

Neutrophil • Granules contain peroxidase, ACP, arylsulfatase
• 50-70% of circulating WBC’s • Other type of granule contains B-glucuronidase, lysozymeandlipase
a. Primary granules ‘contain myeloperoxidase, • Precursor cells of macrophage –monocytes Example:
elastase, proteinase 3, lysozyme, cathepsin G, defensins Alveolar cells – lungs
b. Secondary granules Kuepfer cells – liver
Histiocyte – connective tissue
Collagenase, lysozyme, lactoferrin, plasminogen
activators, ALP, NADPH c. Tertiary Granules Macrophages
Gelatinase, plasminogen activator
• Larger version of monocytes on tissues
• There is increase in the number of ER, lysosomes and mitochondria
• Capable of the process of diapedesis • Granules contain no peroxidase at all compared with monocytes
(Adherence in the wall)
• Monocyte-macrophage system
Pseudopads – false pit Example: -functions in microbial killing, tumoricidal activity, killing of
Chemotactic factor intracellular parasites, phagocytosis, secretion of cell mediators and
antigen presentation. Dendritic Cells
- Neutrophil may wander randomly through the tissue • APC (antigen-presenting cells)
- Can be attracted to specific area - Present antigen to T- cells
- Chemotaxins – chemical messenger causes migration cells - Most potent
Chemotaxis - process • Function is to phagocytosed antigen and present it to T-helper cells
1st stage – margination and adherence 2nd stage – forms •most potent phagocytic cell in the tissues. PRR (Toll-like receptors)
pseudopads through squeeze in junction • Protein discovered in the fruit fly “Drosophila”
3rd stage – chemotaxis if have chemotactic factor Eosinophil
• Similar to molecules found in human leukocyte
• 1-3% of circulating WBCs • Antifungal immunity
• Increases in allergic reactions and parasitic diseases • Highest concentrations in leukocytes
• Reddish-orange granules = Rowaosky’s Stain • It provides surveillance
1. Primary granules • An invariant recognition mechanism that detects specific and
• ACP unique molecular patterns associated with pathogens and
• arylsulfatase inflammation
2. Secondary granules • NBS-LRR proteins (nucleotide-binding site and Leucinerichrepeat) 21
• Major Basic Protein • More than 13 Toll-like receptors
• Eosinophil cationic protein
• Eosinophil peroxidase
• eosinophil-derived neurotoxin
• phospholipase
• histaminase
• aminopeptidase
• ribonuclease
Phagocytosis
ADCC PROCESS
• Engulfment of cells and particulate matter by leukocyte,
- ANTIBODY-DEPENDENT CELLULAR TOXICITY macrophage, and other cells
- Dependent on the antibody Chemotaxis
- Parasite – IgE the granules will poke out and leaves out
- The toxic substance released by the cell are the one killing the
• Cells are attached to the site of inflammation by chemical
substances
microorganism Baophil
Positive chemotaxis: near the site/towards the stimulus
• Less than 1% of circulating WBC’s
Negative chemotaxis: away from the site/ away from the
• Bluish-purple granules contain stimulus Ex: C5a, C5b, C6, C7
- Histamine
- Eosinophil chemotactic factor of anaphylaxis Opsonization
- Heparin • Substances that adhere to antigen to help the phagocyte during the
• Involved in immediate hypersensitive reactions type-1 Mast Cells process of phagocytosis
• Can be found in connective tissues • Coating of antibody and/or complement to facilitate phagocytosis
• Allergic reactions, basophil always pair in mast cells Ex:
• Granules contain 1. C3b
- ACP 2. C4b
- ALP 3. C5b
- Protease Monocytes 4. Fibronectin
5. Leukotrienes
• Largest WBC in the peripheral blood
6. Immunoglobulins
• 4-10% of circulating WBC’s
• No megakaryocytes on peripheral blood if visible, the bone marrow
is affected
 STEPS OF PHAGOCYTOSIS • Tissue damage cause release of vasoactive and chemotactic factors
that trigger a local increase in blood flow and capillary permeability
1. Physical contact between the WBC and the foreign particle • Permeable capillaries allow the influx of fluids and cells
- Through Opsonization or attachment • Phagocytes migrate to the site of the inflammation
- Enhance by opsonin • Phagocytes and anti-bacterial exudates destroy pathogen
2. Formation of phagosome 5 cardinal signs
- Once attachment has occurred, the cellular cytoplasm overflows the 1. Redness (rubor)
particle to form phagosome 2. Calor (heat)
3. Fusion w/ cytoplasmic granule to form phagosome 3. Tumor (swelling)
4. Digestion and release of debris to the outside 4. Dolor (pain)
(exocytosis)
5. Function laesa (loss of function)
Events in Inflammatory Response

1. Rbc’s
2. Vasodilation – increased capillary permeability
3. Adherence of neutrophils Acute Phase Reactants
They are produced by primarily by hepatocytes with 12-24 hours in
response an increase in certain intracellular signaling polypeptides
called cytokines
C-reactive protein

- 6-10 hr
- 0.5 mg/Dl
TYPES OF PHAGOCYTOSIS
- Result in 500 mg/Dl
Indirect
- Non-specific
• Via opsonin receptors that recognize opsonins such as IgG, CRP,
Serum amyloid A
and C3b bound to microorganisms
Direct
- 24 hr
- 3.0
• Via pattern recognition receptors (toll-like) that recognize lipid and
carbohydrate sequences on microorganisms Interferon (IFN)
• Originally named because they literally interfere with viral
PATHWAYS OF KILLING PATHOGENS replication process in an infected cell
• Immunoregulation
Oxygen Dependent • Produced during innate response

Respiratory burst Type 1 IFN or non-immune IFN

- happens on the 2nd stage of phagosome • Produced primarily during initial innate response to viral infection
- occurs when the cytoplasmic pseudopods enclosed the particle • IFN-a: produced by mononuclear phagocytes
within a vaccine • IFN-b: produced by fibroblast
• Hexose monophosphate shunt – utilizes
Type 2 IFN
NADP – NADPH
End product: hypochlorite ions • Also known as immune IFN, because it is primarily produced as a
• The more continues the process, the more toxic to microorganisms component of the specific immune response to viral and other
pathogens
Oxygen Independent
• Also known as gamma-interferon, produced by Tcell r TH1
• there is pathway happen end product formation toxic substance
such nitric oxide Tumor Necrosis Factor
• production of nitric oxide from oxidation of Larginine by NO • Major mediator of the innate defense against gram-negative
synthase which is produced by IFN- gamma activated cells bacteria
• Nitric oxide synthetase is induced when the phagocytic cells come • Induces secretion of APR
in contact with organism Nitric oxide – soluble, highly labile, free
• TNF can also directly trigger apoptotic death of some tumor cells
radical gas that is capable of operating against organisms that
through a receptor-mediated mechanism
invade the cytosol
• In the presence of other reactive oxygen species within the • Pro-inflammatory agent
phagosome, nitric oxide is converted to peroxynitrite another 1. IL-1
product, which are highly toxic to bacteria, yeast, viruses 2. IL-6

INFLAMMATION
3. IL-8 TWO TYPES:
1. TNF-a or cachectin
• The overall reaction of the body to injury or invasion by and
- Produced by macrophages
infectious agent
2. TNF-b or lymphotoxin
• Both cellular and humoral mechanism are involving in this complex
- Produced by CD4+ and CD8+
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- CD4 – T-helper cells (1 &2) - Termed complement was given during 1980’s
- CD8 – T-cytotoxic cells Jules Bordet
COMPLEMENT PATHWAY
- Awarded a noble prize for elucidating the nature of complement
Serum inactivated before run test, we want to inactivate the (1919)
complement system Efects of complement activation:
- Blood, serum, exposed 56 C for 30 mins.
Complement activation promotes
• Complement is a complex series of more than 30 soluble and cell
bound proteins that interact in a very specific way to enhance host • Activation of immune system
defense mechanisms against foreign cells • Opsonization (C3b, C4b, C5b)
• Heat-labile substance • Eventually result to lysis of foreign cells and immune complexes
Paul Ehrlich
Chronic activation: leads to inflammation and tissue damage
Most plasma complement proteins are synthesized in the liver except C1 produced by
epithelial cells and factor D
Factor D – made by adipose tissue
Zymogens – inactive, produce by the liver inactive THREE PATHWAY/WAYS:
1. Classical Pathway
• Pilemer and colleagues discovered an antibody-independent pathway (1950’s)
and this plays a major role as natural defense system
• Properdin system – stabilize C3bBb
2. Lectin Pathway
• Triggers the sugar mannose- (or mannan-) binding lectin (MBL)
• Human do not activate mannose
Adaptive Immunity
• Acquired or specific
• Cellular (t-cell, b-cells, plasma cells)
• Humoral (released by cells) Ex: limpkins and antibodies
Two Types of Adaptive Immunity Active -
Actively involved
1. Natural Active (NAAI)
2. Artificial Active (AAAI)
- Vaccine: antigen (attenuated live vaccine, inactivated, toxoid)
- Ex: BCG vaccine Passive

- Antibodies given by other

1. Natural Passive (NAPI)
- Placental transfer of IgG
2. Artificial Passive (AAPI)
- Vaccine; antibodies - Ex:
anti-rabies
 LYMPHOID SYSTEM
Lymphocytes represent 20-40% of the circulating WBCs
The typical small lymphocyte is between 7 and 10 μm in diameter and has a
large, rounded nucleus that may be somewhat indented Cytoplasm
- is sparse, containing few organelles and no specific granules, and
consists of a narrow ring surrounding the nucleus
• These cells are unique because they arise from a hematopoietic
stem cell and then are further differentiated in the primary
lymphoid organs.
• They can be separated into two main classes, depending on where
this differentiation takes place.
• Lymphocyte circulation is complex and is regulated by different cell
surface adhesion molecules and by chemical messengers called
cytokines
LYMPHOID ORGANS
Primary Lymphoid Organs
• Maturation of the B-cells and T-cells
Bone Marrow = b-cells
Thymus = t cells
Secondary Lymphoid Organs
• Further maturation and proliferation
• It serves as an antigen trapping site when there is an infection
• Potential site in contact with foreign antigen
• Increase the probability of being attacked by t-cells and b-cells
Spleen
Lymph Nodes
Mucosal-associated lymphoid tissue
Appendix
Tonsils
Peyer’s patches – if the antigen is ingested and trapped
in Peyer’s patches
Cutaneous-associated lymphoid tissue
• Infection in the skin, lymph nodes are enlarged
PRIMARY LYMPHOID ORGANS
Bone Marrow
- All lymphocytes arise from pluripotential hematopoietic stem cells
- 1,300 -1500 g (adult)
- Bone marrow fills the core of all long bones and is the main source
of hematopoietic stem cells, which develop into different cell types
• Hematopoiesis happens in the bone marrow
• Hematopoiesis - is the process of
proliferation, differentiation, maturation of specific cell
line
• Activators – they will trigger the bone marrow to commit
itself to producing a specific cell line
- Each of these lines has specific precursors that originate from the
pluripotential stem cells
LYMPHOCYTES & LYMPHOID SYSTEM
- Lymphocyte stem cells are released from the marrow and travel to
additional primary lymphoid organs where further maturation takes
place.
• One subset goes to the thymus and develops into T cells
- In peripheral blood, approximately 10 to 20 percent of all
lymphocytes are B cells, 61 to 89 percent are T cells, and up to 22
percent are NK cells (T-cells --- B- cells --- NK cells)
• 60-80% lymphocytes
• 20-35% peripheral blood 5-10% NK cells
THYMUS
- is an organ which is a small, flat, bilobed organ found in the thorax, or
chest cavity, right below the thyroid gland and overlying the heart
• 30 g (at birth) → 35 g (puberty) → atrophy
• Each lobe of the thymus is divided into lobules filled with
epithelial cells that play a central role in this
differentiation process
• Each lobe of the thymus is divided into lobules filled with
epithelial cells that play a central role in this
differentiation
process
• Mature T
lymphocytes are then
released from the
medulla
SECONDARY LYMPHOID ORGANS
• The secondary lymphoid organs include the spleen, lymph nodes,
tonsils, appendix, Peyer’s patches in the intestines, and other
mucosal-associated lymphoid tissue
• Each lymphocyte spends most of its life span in solid tissue, entering
the circulation only periodically to go from one secondary organ to
another.
 lOMoAR cPSD| 16306511

• A specific lymphocyte may make the journey from blood secondary m and 25 in diameter)
lymphoid organs and back one to two times per day • Lymph nodes are especially numerous near joints and where the
arms and leg join the body
1. SPLEEN
• The lymph fluid flows slowly through spaces called sinuses, which
are lined with macrophages, creating an ideal location for
•Largest secondary lymphoid organ. phagocytosis to take place
- 12cm in length and weighs 150g in adult
REGION OF LYMPH NODES
• `It is located in the upper left quadrant of the abdomen, just below
the diaphragm, and surrounded by a thin connective tissue capsule 1. Cortex
Splenic tissue can be divided into the main types (1) Red pulp Contains macrophages and aggregation of B cells in
(2) White pulp primary follicles, follicular dendritic cells, secondary
follicles (germinal center), plasma cells, and memory
RED PULP
cells
• Makes up more than one-half of the total volume, and its function 2. Paracortex
is to destroy old red blood cells
- All RBCs that need to be sequestered that already reach their
lifespan of 120 days 3. Medulla
• Blood flows from the arterioles into the red pulp and then exits by OTHER SECONDARY ORGANS
way of a splenic vein
WHITE PULP MUCOSAL-ASSOCIATED LYMPHOID TSSUE(MALP)
Appendix
• Comprises approximately 20 percent of the total weight of the
spleen and contains the lymphoid tissue, which is arranged around
arterioles in a periarteriolar lymphoid sheath (PALS) = t-cell zone • Located at the junction of the small and large
area
intestines
o Attached to the sheath are primary follicles
o Surrounding the PALS is a marginal zone containing • Tonsils
dendritic cells that trap antigen
• Lymphoid tissue found in the mucous membrane lining
of the oral and pharyngeal cavities
• Peyer’s Patches
• Are located at the lower ileum of the intestinal tract

CUTANEOUS-ASSOCIATED LYMPHOID TISSUE

(CALT)
- Epidermis contains a number of intraepidermal lymphocytes
- Within each of these secondary organs, T and B cells are segregated
and perform specialized functions
Germinal center – known to contain activated B-cells, secondary follicles
Humoral immunity
2. LYMPH T cells • B cells differentiate into memory cells and plasma cells
NODES zone area and are responsible for humoral immunity or antibody
• Locat production
ed Some T-
along cells, B Cell-mediated immunity
lymp cells and • T cells play a role in cell-mediated immunity, and as
hatic numerous such, they produced sensitized lymphocytes that
ducts plasma secrete cytokines
and
cells
serve “Cytokines are small polypeptides that regulate the functions of lymphocytes
as and other cells involved in the immune response”
centr
al SURFACE MARKER OF LYMPHOCYTES
colle
cting
point - Proteins that appear on cell surfaces can be used as markers to
s for differentiate T cells and B cells
lymp - Such proteins, or antigens, have been detected by monoclonal
h antibodies, which are extremely specific antibodies made by cloning
fluid a single antibody producing wee
from - Several laboratories have developed monoclonal antibodies, and
adjac each used its own nomenclature for the set of antigens found.
ent • Panels of antibodies from different laboratories were
tissu used for analysis, and antibodies reacting similarly with
es standard cell lines were said to define cluster of
(1m diferentiation
 • CD markers used numerical naming - Other surface proteins that appear on the immature B cell include
• These are protein found on the cell surface of any cell CD21, CD 40, and major histocompatibility complex (MHC) class II
• Unique combination of CD markers molecules = antigen recognition
- Mature IgM and cytoplasm disappear
• Can be used to distinguish the developmental stage of
particular cells 4. Mature B cells
- In the spleen, immature B cells develop into mature cells known as
• Cd10 marker – discovered in acute lymphoblastic
marginal zone B cells
leukemia (CALLA) common activated lymphoblastic
- These B cells remain in the spleen in order to respond quickly to any
T AND B LYMPHOCYTES/CELL blood-borne pathogens they may come into contact with
B-cells – differentiate into memory cells and plasma cells and are responsible - Other immature B cells become follicular B cells, which are found in
for humoral immunity or antibody formation lymph nodes and other secondary organs.
- If B cell is stimulated by antigen, it undergoes transformation to a
T-cells – play a role in cell-mediated immunity, and as such, they produce blast stage, which eventually forms memory cells and antibody
sensitized lymphocytes that secrete cytokines in blood circulation: secreting plasma cells
T-cells - Appears IgD cells and IgM on cell surface
B-cells
Activated Differentiation
Differentiation Activated B cells exhibit identifying markers that include CD25,
1. Pro-B cells which is found on both activated T and B cells and acts as a receptor
1st step – is the rearrangement of genes that code for heavy and for interleukin-
light chains of an antibody molecule 2 (IL-2), a growth factor produced by T cells
end result – B lymphocytes programmed to produce a unique PLASMA CELLS
antibody molecule, which consists of two identical light
• Does not undergo replication or proliferation
chains and two identical heavy chains
• Plasma cells are spherical or ellipsoidal cells between 10 and 20 μm
• Heavy chains are coded on chromosome 14 in size and are characterized by the presence of abundant
• Light chains are coded on chromosome 2 and 22 cytoplasmic immunoglobulin and little to no surface
Two types immunoglobulin.
• This represents the most fully differentiated lymphocyte, and its
(1) Kappa chain
main function is antibody production.
(2) Lamdta • Plasma cells are nondividing, and after several days of
- The pro-B cell has distinctive markers that include surface antigens The immature
CD1, CD45R, CD43, and T-cells are
c-kit negative for
- Intracellular proteins found at this stage terminal both Cd4 and
deoxyribonucleotide transferase (TdT) and recombination-
activating genes RAG-1 and RAG2, which code for enzymes involved
in gene rearrangement
2. Pre-B cell
- The first heavy chains synthesized are the μ chains, which belong to
the class of immunoglobulins called IgM = not yet matured
- Pre-B cells also lose the CD43 marker as well as c-Kit and TdT
- Pre-B cells may also express μ chains on the cell surface,
accompanied by an unusual light chain molecule called a surrogate
light chain =
immature
- The combination of the two heavy chains with the surrogate light antibody production, they die without further proliferation
T-LYMPHOCYTES
chains plus two very short chains, Ig-α/Ig-β form the pre-B cell B-CELL DIFFERENTIATION
receptor
- It appears that only pre-B cells expressing the μ heavy chains in
association with surrogate light chains survive and proceed to
further differentiation.
- Once the pre-B receptor (pre-BCR) is expressed, neighboring pre-B
cells may send signals for further maturation
3. Immature B cells
- Rearrangement of genetic sequence coding for light chains on either
chromosome 2 or 22.
- Completion of light chain rearrangement commits a cell to produce
an antibody molecule with specificity for a particular antigen or
group of related antigens.
- Once surface immunoglobulins appear, μ chains are no longer
detectable in the cytoplasm.
- Other surface proteins that appear on the immature B cell include
CD21, CD 40, and major histocompatibility complex (MHC) class II
molecules
 lOMoAR cPSD| 16306511

- The concentration of IgD molecules in the blood is very low =

attached to b-cell mature
- IgM are circulating in the blood
B CELL ACTIVATION

• A significant selection process occurs as maturation takes place, 2. DOUBLE POSITIVE STAGE
because it is estimated that approximately 97 percent of the cortical • Rearrangement of alpha chain Two selection process:
cells die intrathymically before becoming mature T cells (1) positive selection
• 3% of them survive (2) negative selection
• Lymphocyte precursors called THYMOCYTES enter the thymus from
the bone marrow Positive selection
o Within the lobules of the thymus is two • When the CD3-αβreceptor complex (TCR) is expressed on the cell
main zones surface, a positive selection process takes place that allows only
• Outer cortex double-positive cells with functional TCR receptors to survive
• Inner medulla • T cells must recognize foreign antigen in association with class I or
• During development stages, there is an orderly class II MHC molecules
rearrangement of the genes coding for the antigen • Any thymocytes that are unable to recognize self-MHC antigens die
receptor. without leaving the thymus
• At the same time, distinct surface markers appear during Negative selection
specific stages of development.
• Takes place among the surviving double-positive T cells. Cd4 or cd8
• Thymic stromal cells include epithelial cells,
macrophages, fibroblasts, and dendritic cells, all of which • Strong reactions with self-peptides send a signal to delete the
play a role in T-cell development. developing T cell by means of apoptosis, or programmed cell death
• Interaction with stromal cells under the influence of • Most T cells that would be capable of an autoimmune response are
cytokines is critical for growth and eliminated in this
differentiation manner
• This selection process is very rigorous, because only 1 to 3 percent
• A significant selection process occurs as maturation takes
of the double-positive thymocytes in the cortex survive
place, because it is estimated that approximately 97
percent of the cortical cells die intrathymically before 3. MATURE T-CELLS
becoming mature T cells • CD4+ T cells recognize antigen along with MHC class II protein
(PROCESSING AND PRESENTING)
o T helper cells consist of two subsets.
THREE STAGES OF T-CELL DIFFERENTIATION (Th1 and Th2) o They each have a different role to play in
the immune response.
• CD8+ T cells interact with antigen and MHC class I proteins
• Antigen Activation: Antigen must be transported to the T-cell zones
of the secondary lymphoid tissue
• When antigen recognition occurs, T lymphocytes are transformed
into large, activated cells that are characterized by polyribosome-
T-cell filled cytoplasm. Activated T lymphocytes express receptors for IL-2,
immature just as activated B cells do
cells T-REGULATOR CELLS
become
Third major subclass CD4+ T-Cell population
positive to
both cd4 • T-regulatory cells
and cd8 • Suppressing the immune response
1. DOUBLE- • They possess the CD4 antigen and CD25
• These cells comprise approximately 5-10% of all CD4-positive T-cells
NEGATIVE STAGE
• Rearrangemen NATURAL; KILLER CELLS Third population
t of the genes that code for the antigen receptor known as TCR lymphocytes
begins at this stage • 5-10% circulating lymphocyte in the PB
• Beta- chain rearrangement of Signaling by the β chain also triggers • These lymphocytes are generally larger than T cells and B cells at
the thymocyte to become CD4- positive (CD4+) and CD8-positive approximately 15 μm in diameter, and they contain kidney-shaped
(CD8+). nuclei with condensed chromatin and prominent nucleoli
• They have a higher cytoplasmic-nuclear ratio, and the cytoplasm
CD3 - the complex that serves as the main part of the T-cell antigen receptor
contains a number of azurophilic granules
• consists of eight noncovalently associated chains, six of which are
common to all T cells
 • They represent the first line of defense against virally infected and
tumor cells
• Diseases and cancerous cells tend to lose their ability to produce
MHC proteins
ANTIBODY-EPENDENT CELLULAR TOXICITY
A second method of destroying target cells is also available to NK
cells.
o They recognize and lyse antibody-coated cells through a
process called antibodydependent cell cytotoxicity.
o Cells coated with IgM are not subject to ADCC because
IgM has no available Fc region. Primarily IgG is the
antibody responsible for ADCC.
Laboratory techniques to quantify and identify lymphocytes
1. Density Gradient Centrifugation
Ficoll-Hypaque = separate mononuclear cells or the lymphocyte
from other cells
2. Cell Flow Cytometry – any type of cells can be identifying
1. Linear Epitope
• or sequential, where amino acids follow one another on a single chain.
2. Conformational epitope
ANTIGENS AND MHC
NATURE OF ANTIGEN AND MHC
• The immune response of lymphocytes is triggered by materials
• Forward Light scatter: cell size
• Side light scatter: cellular granularity
3. Immunofluorescence Microscopy
• Positive: depend on fluorochrome/ apple green
• Identify and quantify lymphocytes
4. Rosette test/technique
• Lymphocytes are separated from whole blood and then mixed with
suspension of red blood cells
CELL FLOW CYTOMETRY
• An automated system for identifying cells based on the scattering of
light as cells flow in single file through a laser beam
• Fluorescent antibodies are used to screen of subpopulation of T and
B cells Components:
o Sample delivery system o A laser for cell
illumination
o Photodetectors for signal detection of
Computer-based management system IFA –
IMMUNOFLUORSCENCE ASSAY
A. Direct Immunofluorescence
• Use monoclonal antibodies with a fluorescent tag fluorescein and
phycoerythrin (490nm) rhodamine (545nm)
• Detects antigen
B. Indirect Immunofluorescence
• Uses unlabeled antibody that first combines with the antigen by
itself and a second antibody that is complexed with a dye
• Detect antibody
• If negative: free antibody will wash out; no fluorescence will appear
results from the folding of one chain or multiple
TRAITS OF IMMUNOGEN
The ability of an Immunogen to stimulate a host response depends
on the following characteristics:
Macromolecular size of 10000 Dalton or up o If less
than 10,000 = non-
immunogenic
Chemical composition o Made up of proteins and
polysaccharide o
CHON and CHO
Molecular complexity and o the more complex the
structure the more the immunogenicity of the antigen
o the lesser the immunogenicity of antigen
Ability to be processed and presented with MHC
molecules

NATURE OF EPITOPE

• Although an immunogen must have a molecular weight of at least

called “immunogens” 10,000 dalton, only a small part of the immunogen is actually
• The term antigen refers to a substance that reacts with antibody or recognized in the immune response.
sensitized T cells but may not be able to evoke an immune response • Epitopes are molecular shapes or configurations that are recognized
in the first place by B or T cells, and there is evidence that for proteins, epitopes
r
FACTORS INFLUENCING THE IMMUNE RESPONSE e
c
Age
o
Overall health g
Dose n
Route of inoculation i
 lOMoAR cPSD| 16306511

zed by B cells may consist of as few as 6 to 15 amino acids.

• Large molecules may have numerous epitopes, and each one may
be capable of triggering specific antibody production or a T-cell
response
• This key portion of the immunogen is known as determinant site or
epitope
TYPES OF EPITOPES
chains, bringing certain amino acids from different segments of a
linear sequence or sequences into close proximity with each other
so they can be recognized together

RELATIONSHIP OF ANTIGEN TO THE HOST

Autoantigens

• are those antigens that belong to the host

• abnormal
In cases of:
o rheumatoid arthritis osystemic glucose
erythematosus o Type 1 Diabetes
Mellitus o Multiple Sclerosis
Alloantigen’s

• are from other members of the host’s species, and these are
capable of eliciting an immune response.
• They are important to consider in tissue transplantation and in
blood transfusions.
B-cells Heteroantigens
• Surface antibody on B cells may react with both linear and • are from other species, such as other animals, plants, or
conformational epitopes present on the surface of an immunogen microorganisms
• Anything that is capable of crosslinking surface immunoglobulin
• individual exposed to antigen that he/she lacks
molecules is able to trigger Bcell activation.
Heterophile antigens
T-cells
• those that exist in unrelated plants or animals, but which are either
• recognize an epitope only as a part of a complex formed with MHC
identical or closely related in structure so that that antibody to one
proteins on the surface of an antigen-presenting cell.
will cross react with antigen of the other
• T-cell epitopes are linear
• Ex. Polysaccharide type XIV of pneumococcus reacting with anti-A
Haptens antisera
• Some substances are too small to be recognized by themselves, but ADJUVANTS
if they are complexed to larger molecules, they are then able to
stimulate a response. • is a substance administered with an immunogen that increases the
• Haptens are non-immunogenic materials that, when combined with immune response.
carrier, create new antigenic determinants. • It acts by producing a local inflammatory response that attracts a
• they do not meet the minimum 10,000 dalton required large number of immune system cells to the injection site
• they become immunogenic when bind in particles Examples of • It must be injected into the muscle to work
Hapten: Aluminum salts
(1) poison ivy
• when bind on the skin, they become immunogenic • are the only ones approved for clinical use in the United States, and
• leading to conditions contact dermatitis these are used to complex with the immunogen to increase its size
and to prevent a rapid escape from the tissues. Freund’s adjuvant =
(2) drug related
not FDA approved
• drug induced thrombocytopenia = low numbers of platelet
1917 (The specificity of serological reactions) m
ineral oil
• publication of one of the well-known books which study how
Hapten works e
mulsifier
• Dr. Carl Einstein
k
illed
mycobacteria
or Bordetella
0
.5 g/ml
DIFFERENT EFFECTS OF ADJUVANTS o Alleles are alternate forms of a gene that code for
slightly different varieties of the same product. o The MHC
• Forms complex to antigen to increase its size system is described as polymorphic, because there are so
• Prevent rapid escape from tissues many possible alleles at each location.
• Increase processing of antigen
HLA-A has at least 580 different alleles
• Stimulate T-cells that enhance CMI
• Stimulate B-cells enhance HI HLA- B has at least 921 different alleles
• Also stimulates phagocytic cells HLA-C has at least 312 different alleles

MAJOR HISTOCOMPATIBILITY COMPLEX A16 A18

• Evidence now indicates that the genetic capability to mount an
immune response is linked to a group of molecules originally
referred to as Human Leukocyte Antigen
o The French scientist Dausset gave them
this name, because they were first defined by
discovering an antibody response to circulating white
blood cells
• These antigens are also known as MHC, because they determine
whether transplanted tissue is histocompatible and thus accepted or
recognized as foreign and rejected
• MHC molecules are actually found on all nucleated cells in the body,
and they play a pivotal role in the development of both humoral and
cellular immunity
• Gene coding for the MHC molecules in humans are found in the
short arm of chromosome 6.
o Inherited as autosomal dominant gene
o Inherit both genes of both parent
GENES CODING FOR MHC MOLECULES (HLA
ANTIGENS)
• Genes coding for the MHC molecules in humans are found on the
short arm of chromosome 6 and are divided into:
Three categories or classes.
Class 1 molecules
• HLA A, HLA B, and HLA C
• Non classical = HLA E, HLA F, HLA G
• Coded for at three different locations or loci
Class II molecules
• Genes are situated in the D region, and there are several loci
• DQ, DR, DP
• Non classical = HLA DM, HLA DN, HLA DO
Class III molecules
• Genes are located in between class I and class II regions
• To produce complementary proteins C2, C4 and factor B
• Production of cytokines such as TNF
• Involves in antigen recognition
• At each of these loci, or locations, there is the possibility of multiple
alleles.
A19 HLA-A16, 19 HLA-A18,19
A54 HLA-A16, 54 HLA-A18,54
• The probability that any two individuals will express the same MHC
molecules is very low.
• An individual inherits two copies of chromosome 6, and thus there is
a possibility of two different alleles for each gene on the
chromosome, unless that person is homozygous
• MHC alleles are Codominant o They are always expressed in
phenotypic level
• Since the MHC genes are closely linked, they are inherited together
as a package called a haplotype. o Thus, each inherited
chromosomal region consists of a package of genes for A, B, C, DR,
DP, and DQ.
• The full genotype would consist of two of each gene at a particular
locus
STRUCTURE OF MHC CLASS I MOLECULES
• Each of the MHC genes codes for a protein product that appears on
cell surfaces
• All the proteins of a particular class share structural similarities and
are found on the same types of cells.
Class I MHC molecules expressed on all nucleated cells
Alpha folded into three domains a1, a2, a3 planted on cell
membrane
• The a3 region reacts with CD8 on cytotoxic Tcells
• B2-microglobulins does not penetrate the cell membrane but it is
essential for proper folding of a chain
STRUCTURE OF MHC CLASS II MOLECULES
• The occurrence of class II MHC molecules is much more restricted
than that of class I.
• The major class II molecules—DP, DQ, and DR (more polymorphic)
w/ 18 different alleles consist of two noncovalently bound
polypeptide chains that are both encoded by genes in the MHC
complex
DR
• is expressed at the highest level, as it accounts for about onehalf of
all the class II molecules on a particular cell.
o Other class II genes have been
 lOMoAR cPSD| 16306511

described→ DM, DN, and DO (nonclassical) • The main role of the class I and class II MHC molecules is to bind
peptides within cells and transport them to the plasma membrane,
where T cells can recognize them in the phenomenon known as
antigen presentation
CLASS I molecules
• Mainly present peptides that have been synthesized within the cell
to CD8+/T-cytotoxic cell
CLASS II molecules
• Mainly bind exogenous proteins and present it to CD4+/ T-helper
cell
• It is thought that the two main classes of these molecules have
evolved to deal with two types of infectious agents:
o Class I process those infectious agents that attacks from
inside
o Class II process those infectious agents
that attack from the outside

ROLE OF CLASS I MOLECULES

Both MHC class (Class I and II) are synthesized in the rough ER.
Calnexin - it keeps the α-chain in a partially folded state while it awaits binding
to β2–macroglobulin
o three other chaperone molecules— calreticulin,
tapasin, and ERp57—are associated with the complex and help to
stabilize it for peptide binding.
CLASS I HLA CLASS II HLA
Effective for endogenous Effective for exogenous
antigens antigens
• Tumors bacteria
• Viruses
• Parasites
Presented in CD8+ T- Presented in CD4+ Tcytotoxic cells helper cells
Proteasomes/ Invariant chain proteasome maintain
the class
• cylindrical 2; not yet contain accommodated
enzymes that with antigen
process antigen invariant chain peptide
Transporting peptides
• TAP1
• TAP2

ANTIGEN PRESENTATION BY MHC CLASS I

MOLECULE
1ST

• Digestion of these defective or early proteins is carried out by

proteases that reside in large cylindrical cytoplasmic complexes
called proteasomes.
• found on B-cells, monocytes, macrophage, and dendritic cells
• Proteasomes are a packet of enzymes that play a major role in
antigen presentation.
2ND

• Once cleaved, the peptides must then be pumped into the lumen of
the endoplasmic reticulum by specialized transporter proteins.
• These two proteins, transporters associated with antigen processing
(TAP1 and TAP2), = deliver the process antigen to ER where MHC
molecules
• from the cytoplasm to the lumen of the endoplasmic reticulum, of
peptides suitable for binding to class I molecules
• Tapasin→ which helps TAP transporters to have close proximity to
ANTIGEN PRESENTATION
the newly formed MHC class I molecule and mediates interaction
with them so that peptides can be loaded onto the class I molecules.
3RD • Unlike class I molecules, class II molecules must be transported from
the endoplasmic reticulum (ER) to an endosomal compartment
• Once the alpha-chain has bound the peptide, the MHC I-peptide before they can bind peptides
complex is rapidly transported to the cell surface
DENDRITIC CELLS

• are the most potent activators of T cells, and they are excellent at
capturing and digesting exogenous antigens such as bacteria
INVARIANT CHAIN (li)

• prevents interaction of the binding site with any endogenous

peptides in the endoplasmic reticulum
• Ii serves to protect the binding sites
• Once bound to the invariant chain, the class II molecule is
transported to an endosomal compartment, where it encounters
peptides derived from endocytosed, exogenous proteins
• The invariant chain is degraded by a protease, leaving just a small
fragment called class II invariant chain peptide (CLIP) attached to the
ROLE OF CLASS II MOLECULES
peptide-binding cleft
• CLIP is then exchanged for exogenous peptides
lOMoAR cPSD| 16306511
arthritis
Pauciarticular

many cell types and the ability of cytokines to alter expression of numerous genes.
- One pleitropic effect of certain cytokines, is that it can alter the
expression of several genes.
Redundancy
- cytokines that share the same receptor
- Massive uncontrolled overproduction and dysregulation of
cytokines may lead to:
Shock
Multiorgan failure
Death

many cell types and the ability of cytokines to alter expression of numerous
genes.
- One pleitropic effect of certain cytokines, is that it
can alter the expression of several genes.
Redundancy
- cytokines that share the same receptor
- Massive uncontrolled overproduction and
dysregulation of cytokines may lead to:
Shock
Multiorgan failure
Death
CYTOKINES
- are small soluble proteins that regulate the immune system,
orchestrating both innate immunity and the adaptive response to
infection
- are induced in response to specific stimuli—such as bacterial
lipopolysaccharides, flagellin, or other bacterial products— through
the ligation of cell adhesion molecules or through the recognition of
foreign antigens by host lymphocytes.
- The effects of cytokines in vivo include regulation of growth,
differentiation, and gene expression by many different cell types,
including leukocytes
- Individual cytokines do not act alone but in conjunction with many
other cytokines that are induced during the process of immune
activation.
The resulting network of cytokine expression regulates
leukocyte activity and leads to the elimination of the
infection.
Pleiotropic
- nature of cytokine activity relates to the widespread distribution of
cytokine receptors on Autocrine
- affecting the same cell that secreted it.
Paracrine
- affecting a target cell in close proximity
Endocrine - occasionally, cytokines will also exert systemic activities
FEATURES OF CYTOKINES
Pleiotropism
• single cytokine has many different actions
Redundancy
• different cytokines often have very similar effects
Synergy
• cooperative effect of multiple cytokines
Antagonist
• inhibition of one cytokine effects by another cytokine
lOMoAR cPSD| 16306511
CYTOKINES ACTIONS OF CYTOKINES
Act in networks
• stimulate the release of other cytokines
Act as growth factors for hematopoietic cells
• modulate the number and composition of cells
DIFFERENT TYPES/FAMILIES CYTOKINES
TNF
IFN
Chemokines
TGF
CSF
IL
CYTOKINES IN THE INNATE IMMUNE RESPONSE
- Cytokines involved in the innate immune response are responsible
for many of the physical symptoms attributed to inflammation,
such as fever, swelling, pain, and cellular infiltrates into damaged
tissues. Example: Inflammatory agent
- The main function of the innate immune response is to recruit
effector cells to the area.
Cytokines involved in triggering this response are
interleukin-1, tumor necrosis factor-alpha, interleukin-6, chemokines,
transforming growth factorbeta, and interferons-alpha and beta IL-1
Mediator of the innate immune response
Types of IL-1
IL-1α
IL-1β
IL-1RA (IL-Receptor antagonist) - also produced by
monocytes and macrophages.
- This helps to regulate the physiological response to IL-1 and turn off
the response when no longer needed.
TUMOR NECROSIS FACTOR
- Principal mediator of the acute inflammatory response to gram-
negative bacteria and other infectious microbes
- Stimulates gene transcription or induces apoptosis
TNF-
α
- were first isolated from tumor cells and were so named because
they induced lysis in these cells.
- TNF-α exists in both membrane-bound and soluble forms and
causes vasodilation and increased vasopermeability
IL-6
- IL-6 is a single protein produced by both lymphoid and nonlymphoid
cell types.
- It is part of the cytokine cascade released in response to
lipopolysaccharide and plays an important role in acute phase
reactions and the adaptive immune response.
- IL-6 is expressed by a variety of normal and transformed cells,
including T cells, B cells, monocytes and macrophages, fibroblasts,
 hepatocytes, keratinocytes, astrocytes, vascular endothelial cells, - Genes involved in regulation and activation of CD4+ Th1 cells, CD8+
and various tumor cells PLEOMORPHIC ACTIVITIES OF IL-6 cytotoxic lymphocytes, NK cells, bactericidal activities, IL-12R and
• Inflammation IL18R are all regulated by IFN-ɣ.
• Acute Phase Reactions
IFN-ɣ
• Immunoglobulins synthesis prod
• Activation states of B cells and T-cells uctio
• Proliferation and differentiation of B cells into plasma cells n can
CHEMOKINES be
stimu
- Chemokines are a family of cytokines that enhance motility and
promote migration of many types of white blood cells toward the lated
source of the chemokine (chemotaxis). in
- The chemokines are classified into four families based on the matu
position of N-terminal cysteine residues. re
alpha, or CXC, chemokine contains a single amino acid Th1
between the first and second cysteines. cells
Beta or CC, chemokines: —has adjacent cysteine by
residues. two
C chemokines: lacks one of the cysteines. mean
s
CX3C: has three amino acids between the cysteines
(1) l
TGF-B (transforming growth factor beta) i
- TGF- β was originally characterized as a factor that induced growth g
arrest in tumor cells. a
tion of the T-cell receptor (TCR) by MHCpeptide antigen
presentation
(2) cytokine stimulation by IL-12 and IL-18
IFN-α and IFN-β - IL-12 and IL-18 act synergistically to stimulate IFN-ɣ production IL-2
- Were originally named because they literally interfere with viral
replication process in an infected cell - Also secreted by Th1 cells.
- Immunoregulation - IL-2 is also known as the T-cell growth factor
- It drives the growth and differentiation of both T and B cells and
Type 1 IFN or non-immune IFN induces lytic activity in NK cells
- because they are produced primarily during initial innate response TH2 CYTOKINES
to viral infection.
- IFN-α: - IFN-β: IL-4
CYTOKINES IN ADAPTIVE IMMUNE RESPONSE IL-5
IL-10 IL-4
- Adaptive immune response is mainly secreted by T cells, especially T
helper (Th) cells, and affect T- and B-cell function more directly.
- Triggers activation, proliferation and differentiation of B-cells
SUBCLASSES OF T-HELPER - Responsible in allergic reactions, parasitic infections and
TH1 autoimmune disease
- Increases expression of MHC-II on resting B cells
- Th1 cytokines IL-2, IFN-γ - Also induces T-cell proliferation IL-10
TH2 - Inhibits production of pro-inflammatory cytokines by mononuclear
phagocytes
- Th2 cytokines IL-4, IL-5, IL-10 T-reg
- Inhibits the accessory functions of mononuclear phagocytes for T-
TH1 CYTOKINES cell activation
- Dendritic cells in damaged tissues produce IL-12 in response to ERYTHROPOIETIN AND COLONY STIMULATING
certain stimuli such as mycobacteria, intracellular bacteria, and FACTORS
viruses.
- It is also produced by macrophages and B cells and has multiple IL-3
effects on both T cells and natural killer (NK) cells EPO: Erythropoietin
- IL-12 binds to its receptor on naïve T cells and causes the expression
of a new set of genes, including those that determine maturation TPO: Thrombopoietin
into the Th1 lineage IFN- G-CSF: Granulocyte-colony stimulating factor
ɣ
M-CSF: Megakaryocyte-colony stimulating factor
- Produced mainly by Th1 cells
- Stimulates antigen presentation by Class II MHC molecules. GM-CSF: Granulocyte-macrophage-colony stimulating factor
- IgM and IgG only can perform the complement activation Classification:

IgG
IgM
IgA
 lOMoAR cPSD| 16306511

IgD
IgE

TETRAPEPTIDE STRUCTURE OF
IMMUNOGLOBULINS

• All immunoglobulin molecules are made up of a basic four chain

polypeptide unit that consists of two large chains called heavy or H
chains and two smaller chains called light or L chains.
• These chains are held together by noncovalent forces and disulfide
linkage/bond Gerald Edelman and Rodney Portier
- These men shared the Nobel Prize in physiology and medicine
in1972
- They chose to work with immunoglobulin G because they easily
collected than other immunoglobulins
- Edelman’s work centered on using the analytical ultracentrifuge to
separate out immunoglobulins on the basis of molecular weight.
- He found that intact IgG molecules had a sedimentation coefficient
of 7S
The higher the sedimentation rate, the higher the
molecular weight, the larger the molecule
- On obtaining a purified preparation of IgG Edelman used 7M to
unfold the molecule.
- Once unfolded, the exposed sulfhydryl bonds could be cleaved by a
reducing agent such as 2-
Mercapthoethanol
• 3.5 s (approx. 50,000 D; heavy chain)
CHAPTER 4: ANTIBODY STRUCTURE AND FUNCTIONand 2.2 s (approx. 22,000 D; light chain)
• H2L2 = generalized formula for all immunoglobulins

Cleavage with Papein

IMMUNOGLOBULINS • Porter’s work was based on the use of the proteolytic enzyme papain
• Glycoprotein found in the serum portion of the Which was used to cleave IgG
into three blood pieces of about equal size, each having a Composition sedimentation coefficient of 3.5 S and
representing a MW = 45,000-50,000 d
82-96% = polypeptides (protein) He then subjected the immunoglobulin to
2-14% = carbohydrates carboxymethyl cellulose ion exchange
• Electrophoresis (pH 8.6) – immunoglobulins chromatography appears primarily in the gamma region (1) One fragment spontaneously crystallized at 4
• Part of humoral branch of immune response C
• They play an essential role during “antigen (2) The remaining two identical fragments were recognition” and in biological activities related found to
have to immune response such as “Opsonization” antigen-binding
and “complement activation” capacity
- not all immunoglobulins can perform Fab
complement activation fragments
2 Fab and 1Fc Additional fragment called Fc’ was similar to Fc except
that it is disintegrated into several smaller pieces
Each Fab fragment = 1L chain and ½ of H chain Fc = two
halves of chain 1 F(ab)2 and 1Fc

• 1 F(ab)2 = 2 L Chain and 2 halves of H chain

• Fc = two halves of H
Pepsin Digestion
Alfred Nisonof

• Used pepsin to obtain additional evidence for the structure of

immunoglobulins
• This proteolytic enzyme was found to cleave IgG at the carboxy-
terminal side of the interchain disulfide bonds
Yielding one single fragment with MW = 100,000 d and
all antigen-binding ability
known as F(ab)2
 chain ANTIBODY VARIATIONS

Isotype

- a unique amino acid sequence that is common to all

NATURE OF LIGHT CHAIN
The structure of light chains is not fully discovered until the
discovery of an abnormal protein produce by patients with multiple
myeloma.
Bence-Jones Protein
- Found in the urine of patients with multiple myeloma, were in fact L
chains that were being secreted by malignant plasma cells
(overfiltration)
(1) When heated to 60 C, they precipitate from urine
(2) On further heating to 80 C, they redissolve
Analysis of several Bence-Jones proteins revealed that there were
two main types of L chains.
- Designated as kappa (chromosome 2) and lambda (λ) (chromosome
22)
• Each contained between 200 and 220 amino acids, and from
position number 111 on (the amino terminus is position number 1),
it was discovered that each type had essentially the same sequence.
This region was called the constant region
The amino-terminal end was called the variable region Heavy
Chain
• The first approximately 110 amino acids at the amino-terminal end
constitute the variable domain.
• The remaining amino acids can typically be divided up into three or
more constant regions with very similar sequences
• Constant regions of the H chain are unique to each class and give
each immunoglobulin type its name.
IgG has a/a gamma chain γ
IgM has a/a Mu chain μ
IgE has a/an epsilon chain ε
IgD has a/a delta chain δ
immunoglobulin molecules of a given class in a given species
Allotype
- minor variations of these sequences that are present in some
individuals but not others
- Example: IgG subclasses, γ chain known as G1m3 and G1m17
Idiotype
- Variable portions of each chain are unique to a specific antibody
molecule
Hinge Region
• The segment of H chain located between the CH1 and CH2 regions is
known as the hinge region.
• Mainly compose of amino acid proline (IgG, IgD, and IgA has this
region)
It has high content of proline and hydrophobic residues
The high proline content allows for flexibility
The ability to bend lets the two antigenbinding sites
operate independently
It also assists in effector functions such as initiation of
complement cascade Basic immunoglobulin structure
Monomer: has 2 antigen binding sites (2 valence)
• IgG, IgA (in serum portion or plasma), IgM (if bonded or attached on
mature B cells), IgD, IgE
Dimer: has 4 antigen binding sites
• IgA = if they are in secretion
Polymer: more than four antigen binding sites (10 binding sites)
• IgM = seen on secretions (plasma or serum)
Immunoglobulin G
• IgG is the most predominant immunoglobulin in humans.
• 75-805 of the total serum immunoglobulins
• Half-life: 23-25 days
4 Major Subclasses

1. 1Gg1 (67%)
2. IgG2 (22%)
3. IgG3 (7%) – most efficient in complement fixation
4. IgG4 (4%)
• Can cross placenta – All IgG appear to be able to cross the placenta
• Complement fixation
• Opsonization
IgA has a/an alpha chain α • Neutralization of toxins and viruses
• Participation during agglutination and precipitation
 lOMoAR cPSD| 16306511

IgG is most suitable for precipitation than agglutination • It is the second type of immunoglobulin to appear, and it may take a
role in B-cell activation
Immunoglobulin M
• IgM is known as macroglobulin, because it has a sedimentation rate Immunoglobulin E
of 19S, which represents a • The least abundant immunoglobulin in the serum, accounting for
MW of approximately 970,000 only 0.0005% of total serum immunoglobulins
If IgM is treated with mercapethanol, it dissociates into five 7 • The most heat-labile of all immunoglobulins; heating to 56 C for
units, each having a MW of 190,000 and 4-chain structure that between 30 minutes and 3 hours results in conformational changes
resembles IgG and loss of ability to bind target cells
MW (H or m chains) = 70,000 • IgE does not participate in typical immunoglobulin reactions such as
• The pentamer form is found in secretions, while the monomer form complement fixation, agglutination, or Opsonization
occurs on the surface of B cells • IgE may attach to basophils and tissue mast cells by mean of specific
• Half-life: 10 days surface proteins, termed high affinity FC€RI receptors, which are
found exclusively on these cells (during allergic reactions) IgE also
J or Joining chain mediates some types of hypersensitivity (allergic reactions) and
anaphylaxis, and is generally responsible for an individual immunity
- Five monomeric units held together
against invading parasites
- Glycoprotein with several cysteine residues
- Linkage points for disulfide bonds between two adjacent monomers
• IgM assumes a star-like shape with 10 functional binding sites; only
about five of these are used unless the antigen is extremely small
• IgM is found mainly in the intravascular pool and not in other body
fluids or tissues
• It cannot cross to placenta
• IgM is known as the primary response
antibody, because it is he first to appear in the maturing infant
• Found also on the cell surface of B-cells
• Most primitive immunoglobulins Functions:

Fixation
Agglutination
Opsonization, and toxin neutralization

Immunoglobulin A
In the serum, IgA represents 10-15% of all
circulating immunoglobulin, and it appears as a CLASSIFICATION OF
IMMUNOGLOBULINS monomer with MW= 160,000
Two Subclasses (IgA1 = serum or plasma; IgA2 = secretions)

(1) They differ in content by 22 amino acids, 13 of which are located in

the hinge region and deleted in IgA2
(2) IgA2, is found as a dimer along the respiratory, urogenital, and
intestinal mucosa, and it also appears in milk, saliva, tears, and
sweat
• A secretory component which has a mw of about 70,000 is later
attached to the FC region around hinge portion of the alpha chains
• Secretory precursor, with a mw of 100,000 is actually found on the
surface of epithelial cells and serves as a specific receptor for IgA
• Plasma cells that secrete IgA actually home to sub epithelial tissue,
where IgA can bind as soon as it is released from the plasma cells.
Trancytosis
- IgA and SC precursor are taken inside the cell and then released to
the opposite surface by transcytosis.
Immunoglobulin D
• It is extremely scarce in the serum, representing less than 0.001
percent of total IG
• It is synthesized at a low level
• Half-life: 2-3 days
• The MW approximately 180,000, and migrates as fast gamma
protein
• Most of IgD present is found on the surface of immunocompetent
but unstimulated B
lymphocytes
- Attempts to explain the specificity of antibody for a particular antigen
began long before the actual structure of immunoglobulins was discovered
. Erlich’s Side-Chain Theory
• Ehrlich postulates that certain cells had specific surface receptors
for antigen that were present before contact with antigen occurred
• Once antigen was introduced, it would select the cell with the
proper receptors, combination would take place, and then receptors
would break-off and enter the circulation as antibody molecules
Clonal Selection Theory
• In the 1950’s, Niels Jerne and Macfarlane Burnet independently
supported the idea of clonal selection process for antibody
formation
• The key premise is that individual lymphocytes are genetically
preprogrammed to produce one type of immunoglobulin and that a
specific antigen finds or selects those particular cells capable of
responding to it, causing them to proliferate
Template Theory
• Felix Haurowitz
• Second major theory of antibody diversity in
•

1930’s
• Antibody producing cells are capable of synthesizing a generalized
type of antibody, and when contact with an antigen occurs, the
antigen serves as a mold or template and alters protein synthesis so
the antibody with a specific fit is made. This specific antibody
produced enters the circulation, while antigen remains behind to
direct further synthesis Monoclonal Antibody
• George Kohler and Cesar Milstein discovered a technique to
produce antibody arising from a single B cell
- In result, this discovery revolutionized serological testing
Kohler and Milstein’s technique fuses an activated B cell with a
myeloma cell that can be grown indefinitely in the laboratory
- Myeloma cells = lacks an enzyme HGPRT
Hypoxanthine guanine phosphoribosyl transferase

- That renders it incapable of synthesizing nucleotides from

hypoxanthine and thymidine which are needed for DNA synthesis

Hybridoma Production
• One pathway, which builds DNA from degradation of old nucleic
acids, is blocked.
• The other pathway, which makes DNA from new nucleotides, is
blocked by the presence of aminopterin.
• The remaining hybridoma cells are diluted out and placed in

allowed to grow. ANTIBODY DIVERSITY

microtiter wells, where they are

• Each well, containing one clone, is then screened for the presence
of the desired antibody by removing the supernatant.
• Once identified, a hybridoma is capable of being maintained in cell
culture indefinitely, and it produces a permanent and uniform
supply of monoclonal antibody that reacts with a single
epitope
 lOMoAR cPSD| 16306511

Immunology Hepa B vaccine

-study of a host’s reactions when foreign 2. Inactivated vaccine – produced by killing
substances are introduced into the body the organism but capable (typhoid vaccine)
-as a science has its roots in the study of 3. Toxoid vaccine – no longer toxin but
immunity, the condition of being resistant to immunogenic and can be used as vaccine
infection (Diphtheria toxoid vaccine)
Antigen 1885
-foreign substance that induces such as an Pasteur tried out his new procedure to the boy
immune response who was bitten
-all Immunogen are antigen but not all antigen The boy received 12 injections and miraculously
are Immunogen the boy survived
Immunogen – are antigen, macromolecules capable of
triggering adaptive immune response by inducing the Marker
formation of antibodies Fluorescent molecule
Immunity – condition of being resistant to infection Radioactive molecule
1500’s ENZYMES
Chinese developed a practice of inhaling powder
made from smallpox scabs (langib) in order to digestion of microorganisms by hydrolytic enzymes-
produce protection against this dreaded disease excretion of contents of phagolysosome to the outside by exocytosis.
Variolation – exposing an individual to EDWARD Jenner- cross immunity 1798
materials from smallpox lesion LOUIS Pasteur- attenuated vaccine 1880
1700’s CHARLES Columbus
Edward Jenner discovered a relationship A. Old -> New world = smallpox
between exposure to cowpox and immunity to B. New -> old world = syphilis
smallpox Charles Drew
Vaccination – injecting cellular material Blood preservation & transfusion technology
Vacca – Latin word for “cow” Yves La Pierre
Poxviridae -gel tech xm
Smallpox: variola major incubation: 15 minutes
Variola minor infection (known as Alastrim) Mild Smallpox Centrifuge: 10 minutes
Autoimmune diseases MARRY MALLON
Rheumatoid arthritis A cook who died because of typhoid fever during 1492
Systemic lupus
Erythematosus
Rheumatoid Factor An autoantibody found in the serum of most persons with
rheumatoid Arthritis
Autoantibody- An antibody that reacts against person’s own tissue 1st transfusion record
‘With’ autoantibody POPE INNOCENT 7
Rheumatoid Factor- An autoantibody found in the serum of most persons with TARGET CELL OF HIV ‘CD4’
rheumatoid arthritis 2008 Françoise Barré-Sinoussi, Luc Montagnier
Antinuclear antibody (ANA)- An autoantibody directed against a substance in
the cell’s nucleus. Lutheran- donor's name "Luteren"
Cross-immunity
-which exposure to one agent produces protection
against another agen
redness (rubor), swelling (tumor), heat (calor; only applicable to the body'
formation of phagosome- microorganism is completely surrounded by the part
extremities), pain (dolor) and loss of function (functio laesa).
of cell membrane; non-self-material is inside the phagocytic cell
Qualitative-
the antibody against the original antigen also
Positive and negative
works in another antigen
nonreactive or reactive
1880-1881
A scientist works with the bacteria that caused
chicken cholera
VACCINE A SUBSTANCE
Louis Pasteur Quantitative
Development of both microbiology and viral load
immunology SCREENING TEST:
Pasteur applied principle of attenuation to the
prevention of rabies NONREACTIVE AND REACTIVE
AAAI - artificially acquired active immunity
Old culture – can trigger immune response but CONFIRMATORY TESTING:
not capable progress host to disease state
Attenuated, inactivated, and toxoid – type POSITIVE AND NEGATIVE
of virus
1. Attenuated vaccine – not applicable in in contrast, is a type of resistance that is characterized by specificity for each
immunocompromised, low immune system individual pathogen and the ability to
because pathogen is alive remember a prior exposure, which result in an increase response upon
Types of weekend vaccine repeated exposure\allows the body to recognize, remember and respond to a
Sinovac specific stimulus of the antigen
Powerful chemical substances
Cytokine- Powerful chemical substances secreted by cells. Cytokines include All bacilli are gram negative except
lymphokines produced by
Corynebacterium
Lymphokines- Powerful chemicals substances secreted by lymphocytes. These
soluble molecules help Clostridium
direct and regulate the immune responses Mycobacteria
Monokines- Powerful chemical substance secreted by monocytes and
macrophages. These soluble Listeria
Lactobacillus
Erysipelothrix
Bacillus
LARGE
Immunoglobulins- A family of large protein molecules, also known as All spiral organisms are reported gram negative
antibodies.
Macrophage- A larger and versatile immune cell that acts as a microbe- Higher forms of organisms are gram +
devouring phagocyte, an
antigen-presenting cell, and an important source of immune secretions; cell yeast
eating. molds
Monocyte- a large phagocytic white blood cell which, when it enters tissue,
develops into a macrophage actinomyces
Natural killer (NK) cells- large granule-filled lymphocytes that take on tumors Streptomyces
cells and infected body
cells. They are known as “natural” killers because they attack without first Lactobacillus acidophilus
having to recognize specific cortisol- aka stress hormone
antigens physical contact between phagocytic cells and microorganisms or non-self-
Nucleic acids- Large, natural occurring molecules composed of chemical blocks material occurs aided by opsonin (coating of microorganisms)
known as nucleotides. outflowing of cytoplasm- to surround the microorganism (outflowing or
There are two kinds of nucleic acids, DNA and RNA engulfment)
Phagocytes- large white blood cells that contribute to the immune defenses Formation of phagolysosome- cytoplasmic granules fused with cell membrane;
by ingesting microbes or cytoplasmic attach to the microorganism
other cells and foreign particles STEPS OF PHAGOCYTOSIS- ICED
Plasma cells- large antibody-producing cells that develop from B cells 1. INITIATION-
SMALL phagocytosis is initiated as a result of tissue damage, either trauma or as a
B cells- Small white cells crucial to the immune defense. Also known as B result of microorganism multiplication
lymphocytes, they are derived
from bone marrow and develop into plasma cells that are the source of Activated phagocytes have increased surface receptors that allow for
antibodies. adherence.
Lymph nodes- small bean-shaped organs of the immune system, distributed a. CR3
widely throughout the B. Laminin receptor
body and the linked by lymphatic vessels. Lymph nodes are garrisons of B, T, C. Leucyl-formyl-methionyl phenylalanine receptors
and other immune cells
Lymphocytes- Small white blood cells produced in the lymphoid organ’s WITHOUT THE INFLUENCE OF THESE CHEMOTACTIC SUBSTANCES, CELL
paramount in the immune MOTION IS RANDOM
1. Job; s syndrome
defense normal random activity
T cells- Small white blood cells that orchestrate and/or directly participate in abnormal directional chemotaxis
the immune defenses. Also
known as T lymphocytes, they are processed in the thymus and secrete 2. Lazy leukocyte syndrome
lymphokines Abnormal random chemotaxis
african Trypanosomiasis, also known as “sleeping sickness”, is caused by 3. Engulfment-- final structure is known as phagosome or phagocytic structure
microscopic parasites of the species Trypanosoma brucei. It is transmitted by by active amoeboid motion
the tsetse fly (Glossina species), which is found only in sub-Saharan Africa. phagolysosome- fuse and rupture release enzyme that will digest particle
trichinella spiralis Opsonins (antibodies and complement components) interact with the surfaces
of bacteria. rendering them acceptable to the phagocyte
Neutrophil increase- Bacteria A. Exhibited by a large capsule:
Lymphocytes increase- Viral - H. influenzae
Monocytes increase- infection -N. meningitidis
-S. Pneumoniae
The general rule for micro ^all causes meningitis
minute cell particles that contain hydrolytic enzymes and peroxidase approach
All cocci are gram positive except the phagosome, fuse with it, rupture, and discharge contents to it.
Neisseria minute cell particles that contain hydrolytic enzymes and peroxidase approach
the phagosome, fuse with it, rupture, and discharge contents to it.
Branhamella cells become degranulated as foreign materials are digested
Moraxella high density lipoprotein
reticuloendothelial system
Veilonella Fibrinogen most abundant coagulation factor
A coagulation factors
 lOMoAR cPSD| 16306511

Wilson disease is a rare genetic disorder characterized by excess copper stored Type I hypersensitivity reactions involve the activation of tissue mast cells and
in various body tissues, particularly the liver, brain, and corneas of the eye blood basophils when IgE molecules bound to their surface become linked
Mannose binding protein also called mannose binding lectin together by an allergen. Substantial numbers of individuals develop allergies
due to type I (IgE-mediated) hypersensitivity, also referred to as atopic allergy.
Dendritic Cells APC (antigen-presenting cells) - Present antigen to T- cells -
Most potent Function is to phagocytosed antigen and present it to T-helper
cells •most potent phagocytic cell in the tissues.
IgE- allergic response
IgA- saliva and tears
3rd line of defense
Elf discrimination
Memory
cytokines- long lived
antibodies- short lived

Celular defense mechanism

Cells involve non speci
phil 50-70% of circulating WBC’s a. Primary granules ‘contain myeloperoxidase,
elastase, proteinase 3, lysozyme, cathepsin G, defensins b. Secondary granules
Collagenase, lysozyme, lactoferrin, plasminogen activators, ALP, NADPH c.
Tertiary Granules Gelatinase, plasminogen activator
Capable of the process of diapedesis (adherence in the wall) Pseudopods –
false pit Example: Chemotactic factor - Neutrophil may wander randomly
through the tissue - Can be attracted to specific area - Chemotaxins – chemical
messenger causes migration cells Chemotaxis - process 1 st stage – margination
and adherence 2 nd stage – forms pseudopods through squeeze in junction 3
rd stage – chemotaxis if have chemotactic factor Eosinophil 1-3% of circulating
WBCs Increases in allergic reactions and parasitic diseases Reddish-orange
granules = Rowaosky’s Stain 1. Primary granules ACP arylsulfatase 2. Secondary
granules Major Basic Protein Eosinophil cationic protein Eosinophil
Capable of the process of diapedesis (adherence in the wall) Pseudopods –
false pit Example: Chemotactic factor - Neutrophil may wander randomly
through the tissue - Can be attracted to specific area - Chemotaxins – chemical
messenger causes migration cells Chemotaxis - process 1 st stage – margination
and adherence 2 nd stage – forms pseudopods through squeeze in junction 3
rd stage – chemotaxis if have chemotactic factor Eosinophil 1-3% of circulating
WBCs Increases in allergic reactions and parasitic diseases Reddish-orange
granules = Rowaosky’s Stain 1. Primary granules ACP arylsulfatase 2.
Secondary granules Major Basic Protein Eosinophil cationic
protein Eosinophil peroxidase eosinophil-derived
neurotoxin phospholipase histaminase aminopeptidase ribonuclease ADCC
PROCESS - ANTIBODY-DEPENDENT CELLULAR TOXICITY - Dependent on the
antibody - Parasite – IgE the granules will poke out and leaves out - The toxic
substance released by the cell are the one killing the microorganism
Basophil Less than 1% of circulating WBC’s Bluish-purple granules contain -
Histamine - Eosinophil chemotactic factor of anaphylaxis - Heparin Involved in
immediate hypersensitivity reactions type-1 Mast Cells Can be found in
connective tissues Allergic reactions, basophil always pair in mast
cells Granules contain - ACP - ALP - Protease Monocytes Largest WBC in the
peripheral blood
Ground glass appearance
4-10% of circulating WBC’s
peroxidase eosinophil-derived
neurotoxin phospholipase histaminase aminopeptidase ribonuclease ADCC
PROCESS - ANTIBODY-DEPENDENT CELLULAR TOXICITY - Dependent on the
antibody - Parasite – IgE the granules will poke out and leaves out - The toxic
substance released by the cell are the one killing the microorganism
Basophil Less than 1% of circulating WBC’s Bluish-purple granules contain -
Histamine - Eosinophil chemotactic factor of anaphylaxis - Heparin Involved in
immediate hypersensitivity reactions type-1 Mast Cells Can be found in
connective tissues Allergic reactions, basophil always pair in mast
cells Granules contain - ACP - ALP - Protease Monocytes Largest WBC in the
peripheral blood 4-10% of circulating WBC’s