IMMUNITY

Immunity
● Also known as "resistance"
● Your immune system is your body's defense mechanism against
harmful microbes or environmental agents
● Susceptibility: lack of immunity

First Line of Defense

*if this fails, ur body then relies to the immune system

Physical Factors
● Skin
○ Dermis- inner portion made of connective tissue
○ Epidermis - outer portion, with epithelial cells containing keratin
○ Shedding and dryness of skin inhibits microbial growth
● Mucous membranes
○ Lines Gl, respiratory and GU tracts
○ Mucus - viscous glycoproteins that trap microbe and prevent
tracts from dying out
○ Lacrimal apparatus - drains tears; washes eye
● Ciliary escalator - transports microbes trapped in mucus away from
the lungs Innate immune response USUALLY goes first in combating a potential
● Earwax prevents microbes from entering the ear microbial invasion
● Urine cleans the urethra by flow While there are resident cells in the “both” category in organs,
● Vaginal secretions move microorganisms out of the vaginal tract differentiation into macrophages, dendritic cells, etc. can be trigged by the
● Peristalsis, defecation, vomiting, diarrhea presence of pathogen associated chemical signals in the body or by
chemical signals from other cells
Chemical factors
● Sebum - forms a protective film and lowers pH of skin NOTES
● Lysozyme - found in sweat, tears, saliva, and urine; destroys bacterial ● eosinophil - oxidative burst - removes toxins from oxygean
cell walls ● antigen- targets of viruses
● pH 1.2-3.0 of gastric juice destroys most bacteria and toxins ● monocyte -. precursor cells like stem cells - can turn into other cell
● pH 3-5 of vaginal secretions inhibits microbes types
● natural killer cell - infected cells
Two Types of Immunity ● t helper cells - activates other cells (t cells cant do anything unless
● Innate Immunity - Defenses that are present at birth; rapid initial activated)
response to an invading microbe - WBC ● cytotoxic cell - kills cells
- Innate immune cells are already active ● granulocytes - have granules and histamines
Not specialized - generalized immunity
Antibodies and t cells are specific to the pathogen that it is
targeting. But innate immunity is not

● Adaptive Immunity - Defenses that are produced specifically for a

particular microbe that has breached innate immunity. Slower to
respond but has "memory" that allows efficient microbe suppression. -
vaccines - better for virus like covid than innate immunity
● Specifically targeting against specific pathogens

● Cellular Immunity - Cellular immunity is a protective immune process

that involves the activation of phagocytes, antigen-sensitized if results are different from this, the body is already immunocompromised
cytotoxic T cells and the release of cytokines and chemokines in
response to antigen (i.e. an immune response that primarily involves Hematopoesis
cells). • Hematopoiesis is the production of all of the cellular components of
blood and blood plasma. It occurs within the hematopoietic system, which
● Humoral Immunity - aspect of immunity that is mediated by includes organs and tissues such as the bone marrow, liver, and spleen.
macromolecules - including secreted antibodies, complement • It is the process by which the body manufactures blood cells
proteins, and certain antimicrobial peptides - located in extracellular • While the liver, spleen, and other components of the hematopoetic
fluids (i.e. an immune response that involves macromolecules found in system do produce and store immune cells, most immune cells (leukocytes)
the body's humors (fluids). are produced in the bone marrow.
- everything that is not a cell “Leukocyte” is the proper term for white blood cell
White Blood Cells (Leukocytes) Innate Immunity
• Granulocytes - are leukocytes with granules in their cytoplasm that are INFLAMMATION
visible with a light microscope • In the context of immunity, inflammation is the process by which immune
● Neutrophils - phagocytic; work in early stages of infection cells are transported to the site of an infection or injury.
● Basophils - release histamine; work in allergic responses • Signs and symptoms: pain, redness, immobility, swelling (edema, caused
● Eosinophils - phagocytic; toxic against parasites helminths by leakage of blood plasma into tissue), heat
• Agranulocytes - leukocytes with granules in their cytoplasm that are not • Destroys injurious agent or limits its effects on the body
visible with a light microscope • Repairs and replaces tissue damaged by the injurious agent
● Monocytes - mature into macrophages in tissues where they are • Inflammation activates acute-phase proteins by the liver that cause
phagocytic vasodilation and increased permeability of blood vessels
● Dendritic cells - found in the skin, mucous membranes, and
thymus; phagocytic
● Lymphocytes - T cells, B cells, and Natural Killer (NK) cells; play
a role in adaptive immunity

● WILL COME OUT AT THE END TERM

● receptors from the cells attached to the pathogens to recognize it
● phagocytes are the first cells to go to the bacterial site, and if the
phagocytes can deal with the problems then go back to the
blood stream, it shows that we dont need adaptive immunity
● phagocytes will stick then the blood vessels will dilate to allow
them to squeeze through

When you are sick, innate immune cells already resident in the tissue will
pick up on molecular patterns when they pick up the secretions from the
pathogen - how they sense bacteria and then send chemical signals to call
other innate immune cells to come to the area who will eat the bacteria
before going back to the blood stream and it takes to the lymph nodes
where the adaptive immune cells are-

Pathogen Recognition Receptors (PRRS)

● Toll-like receptors (TLRs) - proteins found on host cells
● Attach to pathogen-associated molecular patterns (PAMPs)
● PRRs bound to PAMPs induce cytokine release from host cell;
regulate intensity and duration of immune responses
● attach to pathogen & recognize them to stimulate immune
response

Many different types of molecules govern the differentiation of stem cells

into leukocytes, not all of these molecules have been identified
- Resident immune cells and damaged cells release these
molecules upon the binding of PAMPs to their PRRs in order to
pluripotent - means they can become a lot of things recruit more immune cells to the site of the infection/injury (i.e.
all stem cells come from pluripotent stem cells induce inflammation).
- it is possible to make many kinds of cells from pluripotent stem - During the initial stages of an infection (i.e. the stage where the
cells innate immune response is most prevalent), most of the cells
recruited to the site of the infection/injury will be phagocytes (i.e.
macrophages, dendritic cells, and neutrophils).
CYTOKINES ● This process is carried out by phagocytes (i.e. macrophages,
● Cytokines are chemical messengers produced in response to a neutrophils, and dendritic cells).
stimulus
● Interleukins (ILs): cytokines between leukocytes Mechanism of Phagocytosis
● Chemokines: induce migration of leukocytes interferons (IFNs): Chemotaxis
interfere with viral infections of host cells - Chemical signals attract phagocytes to microorganisms
● Tumor necrosis factor alpha (TNF-a): involved in the inflammation of (messengers)
autoimmune diseases Adherence
● Hematopoietic cytokines: control stem cells that develop into red - Attachment of a phagocyte to the surface of the microorganism
and white blood cells - when the body needs more t cells, they are the Ingestion
ones to tell the stem cells that they need to make t cells - Opsonization: microorganism is coated with serum proteins,
● Chemical signals is how the cells talk to each other - so when they makin ingestion easier
sense bacteria, they release cytokines which held other cells in the Digestion
body - - Microorganism is digested inside a phagolysosome

Phagocytes (Phages)
• Phago - from the Greek, meaning eat
● Cyte - from the Greek, meaning cell
● Fixed phagocytes are residents in tissues and organs
● Free (wandering) phagocytes roam tissues and gather at sites
of infection
- Phagocytes are attracted to site of infection via chemical signals
Phagocyte Migration and Phagocytosis - Microorganisms can be coated with opsonins
- Margination - sticking of phagocytes to blood vessels in attach- eat - digest - take digestive enzymes then take antigen then take
response to cytokines at the site of inflammation MHC - Then shown to the t cells
- Phagocytes squeeze between endothelial cells of blood vessels
via diapedesis Interferons
● Cytokines produced by cells; have antiviral activity
● IFN-a and IFN-B: produced by cells in response to viral infections;
cause neighboring cells to produce antiviral proteins (AVPs) that
inhibit viral replication
● IFN-y: causes neutrophils and macrophages to kill bacteria

Antimicrobial peptides
● Short peptides produced in response to protein and sugar molecules
on microbes
- Inhibit cell wall synthesis
- Form pores in the plasma membrane
● Broad spectrum of activity
● Produced primarily by mast cells.

Other associated processes

Tissue Repair
● Cannot be completed until all harmful substances are removed or
neutralized
● Blood clot seals off site of entry ● Stroma is the supporting connective tissue that is repaired
● Abcess is a collection of immune cells, bacteria, and cellular debris ● Parenchyma is the functioning part of the tissue that is repaired
● keep the bacteria localized (picture) Fever
● Abnormally high body temperature
PHAGOCYTOSIS ● Produced in an attempt to heat-kill harmful microbes and induce
● Phagocytosis is a cellular process for ingesting and eliminating increased immune cell activity
particles larger than 0.5 μm in diameter, including microorganisms, ● Hypothalamus is normally set at 37°C
foreign substances, and cells that have undergone apoptosis ● Cytokines cause the hypothalamus to release prostaglandins that
(programmed cell death). reset the hypothalamus to a higher temperature
● The body maintains the higher temperature until the cytokines are
eliminated
● As body temperature falls (crisis), vasodilation and sweating
occurs
Adaptive Immunity MHC Mechanism
● When a macrophage engulfs a microorganism, it partially digests it
Lymphatic System and displays peptide fragments of the microbe on its surface, bound
● The lymphatic system is a network of delicate tubes throughout to MHC II molecules.
the body. ● T lymphocytes recognize the foreign fragment attached to the MHC II
● It drains fluid (called lymph) that has leaked from the blood molecule and binds to it, stimulating an immune response.
vessels into the tissues and empties it back into the bloodstream ● Self-antigens are presented on MHC I molecules on the surface of
via the lymph nodes. infected host cells.
● Lymph, lymphatic vessels, lymphoid tissue, and red bone marrow
● Contains lymphocytes and phagocytic cells
● Lymph carries microbes to lymph nodes where lymphocytes and
macrophages destroy the pathogen

T-Cells
● also called T lymphocyte, they are a type of leukocyte that is an
Lymphocytes essential part of the adaptive immune system.
● Cells that are present throughout the lymphatic system (i.e. B-cells, ● They originate in the bone marrow and mature in the thymus.
T-cells, and NK-cells). ● In the thymus, T-cells differentiate into two main types: T-helper cells
● B-cells and T-cells are the primary cell types that mediate adaptive (CD4+ T-cells) or Cytotoxic T-cells (CD8+ T-cells).
immunity. ● T-cells bind to antigens expressed on the MHC using the T-cell
● Activated via antigen presentation from phagocytes and other innate receptor.
immune cells that have entered the lymph nodes. ● CD4 and CD8 are glycoproteins expressed on the surface of the
surface of their associated T-cell and serve as co-receptors for the
T-cell receptor.
● There are also regulatory and memory T-cells but they are not very
well understood.

Major Histocompatibility Complex

● Major histocompatibility complex (MHC) is group of genes that code
for proteins found on the surfaces of cells that help the immune
system recognize foreign substances.
● There are two major types of MHC protein molecules—class I and
class II.
● Class I MHC proteins are found on the membranes of almost every
cell in the body.
● Class II MHC proteins are only found on the membranes of CD8+ T-cell mediated cell death: Perforin-Granzyme Pathway
marcophages and lymphocytes.
Th1 vs. Th2 immune responses
● Th1 –mediated responses are initiated in response to intracellular
pathogens such as bacteria and viruses and are primarily
pro-inflammatory
● Th2 –mediated responses are initiated in response to extracellular
pathogens such as parasites and are primarily anti-inflammatory
● Each response may be initiated by the same types of cells, but each
has its own set of cytokines and other chemical signals.
B Cells
● B lymphocytes are produced in the bone marrow and mature in the
spleen.
● B cells are responsible for mediating the production of
antigen-specific immunoglobulin (Ig) directed against invasive
pathogens (typically known as antibodies).
● B Cells bind antigens via the BCR (B-cell receptor) expressed on their
surface.
● B-cells can bind either extracellular pathogens or pathogens
presented by antigen presenting cells like phagocytes
● CD4+ T-cells can bind to the antigen presented on the BCR and
release cytokines that will activate the B-cell.

Antigens and Antibodies

B-Cell Differentiation ● Antigens: substances that cause the production of antibodies
● Once activated, B-cells can differentiate into either Plasma cells or ● Usually components of invading microbes or foreign substances
Memory B-cells. ● Antibodies interact with epitopes, or antigenic determinants, on
● Plasma B-cells produce antibodies to fight off a currently active the antigen
infection. ● - Difference between epitope and antigen
● Memory B-cells remain dormant in the bloodstream until they are
again activated by cytokines

Clonal Selection/Deletion
● Clonal selection differentiates activated B cells into:
○ Antibody-producing plasma cells
○ Memory cells
● Clonal deletion eliminates harmful B cells via apoptosis.
- What would be an example of a harmful B-cell

Antibodies
● Globular proteins called immunoglobulins (Ig)
● Valence is the number of antigen-binding sites on an antibody
○ Bivalent antibodies have two binding sites
● Four protein chains form a Y-shape
○ Two identical light chains and two identical heavy chains joined
by disulfide links
○ Variable (v) regions are at the ends of the arms; bind
epitopes
○ Constant (Fc) region is the stem, which is identical for
IgA is first line of defense but not first antibodies produced (prevents
a particular Ig class
bacterial and viral adhesion to host surfaces)
■ Five classes of Ig (IgG, IgM, IgA, IgD, IgE)
 Immunological Memory
T-dependent vs. T-independent Antigens ● Secondary (memory or anamnestic) response occurs after the second
T-dependent antigen exposure to an antigen
● Antigen that requires a CD4+ cell to produce antibodies ○ Class switching, where initial IgM response shifts to
T-independent antigens IgG, IgE, or IgA, occurs
● Stimulate the B cell without the help of T cells ○ More rapid, lasts many days, greater in magnitude
● Provoke a weak immune response, usually producing IgM ○ Memory cells produced in response to the initial
● No memory cells generated exposure are activated by the secondary exposure
● Antibody titer is the relative amount of antibody in the serum
○ Reflects intensity of the humoral response
● - What B cells are responsible for the memory response?

Results of the Antibody-Antigen complex

● An antigen–antibody complex forms when antibodies bind to antigens
● Strength of the bond is the affinity
● Protects the host by tagging foreign molecules or cells for
destruction
● Agglutination
● Opsonization
● Antibody-dependent cell-mediated cytotoxicity
● Neutralization
● Activation of the complement system

IgA is first line of defense but not first antibodies produced (prevents
bacterial and viral adhesion to host surfaces)
Antibody Class Switching

● Which region do we have to change to switch the class of an

antibody?
● Constant heavy region is changed, variable region stays the same
● Class switching does not change what antigens the antibody binds to, ● Innate immune response USUALLY goes first in combating a
but it does change what effector molecules it interacts with potential microbial invasion
● While there are resident cells in the “both” category in organs,
What causes class switching? differentiation into macrophages, dendritic cells, etc. can be
● Naïve, mature B cells produce IgM and IgD, which are the first trigged by the presence of pathogen associated chemical signals
two heavy chain segments in the Immunoglobulin locus. in the body or by chemical signals from other cells
● After activation these B cells proliferate.
● When they encounter specific cytokines or other signaling Natural-Killer (NK) Cells
molecules (usually produced y CD4+ T-cells), they undergo class ● Granular leukocytes that destroy cells that don't express MHC class I
switching into IgG, IgA, or IgE antibody producing B cells. self-antigens (“Missing Self Hypothesis”)
● Kill virus-infected and tumor cells and attacks parasites
Heavy chain exons: ● Form pores in the target cell (via perforin-granzyme pathway), leading
μ - IgM to lysis or apoptosis
δ - IgD
γ3 - IgG3
γ1 - IgG1
α1 - IgA1
γ2 - IgG2
γ4 - IgG4
ε - IgE
α2 - IgA2

● Which other cells destroy MHC class I cells?

● Some intracellular pathogens and microbes downregulate MHCI
● Exons vs expression
introns (stop codons)
● Restriction endonuclease Mast Cells
● Homologous repair requires a template ● Mast cells are granulocytes and are among the first line of defense
against antigens entering the body since they are localized in mucosal
and epithelial tissues and do not remain in the blood.
● In innate immunity, receptors on mast cells bind to antigens, causing a
release of inflammatory mediators like IL-4, TNFα, IL-6, IFN-α and
IFN-β.
● In adaptive immunity, mast cells process and present antigen via
MHCI and MHCII.
● Mast cells are also involved in an allergic reaction where the
over-activation of mast cells can result in hyper-allergic reactions (via
IgE response).
● IgE response displayed by these cells is also used in response to
parasites.
 ○ Antibodies bind to antigens, activating C1
○ C1 splits and activates C2 and C4
○ C2a and C4b combine and activate C3
○ C3a functions in inflammation
○ C3b functions in cytolysis and opsonization
● The Alternative Pathway
○ C3 present in the blood combines with factors B, D,
and P on microbe surface
○ C3 splits into C3a and C3b, functioning the same as in
the classical pathway

Eosinophils
● Eosinophils are the primary cells in the immune response to parasitic
infections.
● Eosinophil granules contain a variety of proteins, cytokines, and
enzymes that are involved in not only responding to a parasitic
infection, but also in asthma and allergic responses.
● An accumulation of Eosinophils in the nasal mucosa is a major
indicator of allergic rhinitis.

● Membrane attack complex forms pores that allow extracellular

Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC)
fluids into the cell to pop it like a balloon
● C3 combines with B,D, and P on the microbe surface then splits

The Lectin Pathway

● Macrophages ingest pathogens, releasing cytokines that
stimulate lectin production in the liver.
● Mannose-binding lectin (MBL) binds to mannose, activating C2
and C4.
● C2a and C4b activate C3, which functions the same as in the
classical and alternative pathways.
● TCC (Terminal Complement Complex) is another name for MAC
● MBL activates MASP1 which activates MASP2 which activates
C2 and C4

Basophils
● Like Mast cells and eosinophils, basophils play a role parasitic
infections and allergies.
● Basophils have receptors on their surface that bind IgE (like mast
cells).
● Basophil granules contain histamine (vasodilator) and heparin
(anticoagulant).
● - What are vasodilators and anticoagulants and how would these
contribute to the immune response?

The Complement System

● Serum proteins produced by the liver that enhances the immune
system in destroying microbes
● Act in a cascade in a process called complement activation
● Proteins are designated with uppercase C and numbered in order of
discovery
● Activated fragments are indicated with lowercase a and b
● The Classical Pathway
 ● C5a and C3a can activate mat cells
● C5a is a chemoattract for phagocytes

The Complement System and Disease:

1. Regulation of complement
- Regulatory proteins readily break down complement proteins,
minimizing host cell destruction
2. Complement and disease
- Lack of complement proteins causes susceptibility to infections
3. Evading the complement system
- Bacterial Capsules prevent complement activation

Immunodeficiencies
● Absence of a sufficient immune response
● Congenital immunodeficiencies: due to defective or missing
genes
● Acquired immunodeficiencies: develop during an individual’s life
● Due to drugs, cancers, and infections