IMUNE SYSTEM &

IMUNE RESPONSE
Eka Yunita Amna
 Definition

Immunity is a function of which an

individual recognizes and excludes antigenic
foreign substances
Immune responses: host reactions against antigens ; reactions
are mediated by components of the immune system
Immunity
Factors Modify Defense Mechanisms

Age
Hormones
Drugs and chemicals
Malnutrition
Fatigue and stress
Genetic determinants
 Innate
immunity

 Exists naturally
 Non–specific
 No immune memory (innate immunity can’t be
enhanced by the second stimulation of the same
antigen)
 Hereditable
 No racial difference
 Innate
(1) Barriers immunity
 Physical barrier : skin and mucosa
 Chemical barrier: antimicrobial substances in secretion of
skin and mucosa
 Biotic barrier: normal flora existing on the surface of skin
and mucosa
 Anatomic barrier (2) Humoral factors
. blood- brain barrier  Complement
. blood- placental barrier
. blood- tymus barrier  Lysozyme
 Interferons(IFN)
 C-reactive protein
 Intact Skin
• Difficult for a pathogen to penetrate
– Sweat creates high salt conditions
– Oil layer, fatty acids and acid pH present makes an
inhospitable environment for microorganisms
• Normal flora prevent other microorganisms
from establishing an infection – “competitive
exclusion”
Physical barriers – Intact Skin
 Natural Immunity etc...
• Stomach acid (HCl) kills pathogens and sterilizes food.
• Mucus lining of lungs traps pathogens and cilia move particles
out to throat and it is swallowed.
• Coughing and sneezing.
• Tears wash away pathogens and have bacteriocidal enzymes.
• Flushing action of urine
• Circulating cells and tissue cells
• Wax in ears
• Normal flora prevents growth of opportunistic pathogens in
mouth, large intestine and reproductive system
Natural Immunity - Cilia
 Innate
immunity

(3)Cells participating in innate immunity

 Phagocyte: endocytosis and phagocytosis
mononuclear phagocytes
----Monocytes,Macrophages
Neutrophils
 Nature killer cells (NK)—KAR/KIR,IgG Fc receptor
 Dentritic cells(DC)
 γδ T cells
 B1 cells
 Other cells participating in innate immunity
 Second Line of Defense

If microbes are not successfully killed locally, may

further invade the host by way of the lymphatics to the
regional lymph nodes
• within lymph nodes the bacteria meet other phagocytic cells
• bacteria may overcome these and gain access to the bloodstream
where they meet circulating phagocytes (neutrophils and monocytes)
• may pass through the bloodstream and reach organs such as the liver
and spleen where they come into contact with tissue macrophages
• although a powerful defense system, this final phagocytic barrier may
be overcome, with seeding of the microorganism to organs such as
bone, brain, and kidney, terminating in fatal septicemia
 Nonspecific Immunity: internal

Inflammatory response - four classic signs are

redness, swelling, heat and pain.
• Dilation of capillaries (hyperemia) to increase blood flow to
area
• Chemotaxis - chemicals released which cause phagocytic white
cells to migrate to the area.
• Increased capillary permeability allowing white cells to go to
injured area, a process known as “diapedesis”
• Formation of exudate - same composition as plasma and it
contains antibacterial substances, phagocytic cells, and drugs
and antibiotics, if present.
Inflammatory Response
Inflammatory Response - Phagocytosis

1.Initiation is caused by damage to the tissues,

either by trauma or as a result of microbial
multiplication.
2.Chemotaxis, attraction of leukocytes or
other cells by chemicals.
3.Opsonization - Opsonization coating a
pathogen by substances so as to enhance
4. Adherence - firm contact between
phagocytosis.
phagocyte and microorganism.
5.Engulfment into cytoplasm and
enclosed in a vacuole.
6.Digestion enzymatic contents in vacuole
destroy the microorganism.
Number of killing mechanisms operating
in the vacuoles of phagocytic cells.
One of the major mechanisms involves
hydrogen peroxide which, acting along
with an intracellular enzyme, is rapidly
lethal to many bacteria.
 Inflammation

Chemokines Inflammatory cells

migrate into tissue,
releasing inflammatory
mediators that cause
Cytokines
pain

Bacteria
trigger
macrophages
to release
Proteins
cytokines and
chemokines Fluids
Vasodilation and
increased vascular
premeability cause
redness, heat, and
swelling
 Phagocytic Cells

• Mononuclear phagocytes - include both circulating blood

monocytes and tissue macrophages found in various tissues
of the body.
– Arise from bone marrow stem cells
– Not end cells, they may divide.
– Ingest and destroy material such as bacteria, damaged host cells or
tumor cells (non-specific immunity).
– Stay in peripheral blood 70 hours - migrate to tissues, double in size,
then called tissue macrophages.
– Tissue macrophages named according to tissue location- liver=Kupffer
cells, brain-microglial cells, etc.
– Phagocytosis takes place to a greater degree in tissues.
Monocyte and Tissue Macrophage
Macrophages
Macrophages excluding the pathogen
 Neutrophils
• Characterized by a large nucleus, 3 - 5 lobes,
and specific granules in the cytoplasm.
• Arise from bone marrow stem cells.
• They are end cells.
• Primary function is ingestion (phagocytosis).
• Clear body of debris such as dead cells and
thrombi.
• Able to move into tissues by diapedesis.
Neutrophils with Ingested Material
Neutrophil Involved in Phagocytosis
 Eosinophils
• Easily distinguished by the presence of large granules in their
cytoplasm which appear red when stained by routine
hematology stains.
• Much less phagocytic than macrophages or neutrophils
• Function is far from clear, however the numbers increase
greatly in certain parasitic diseases and allergic diseases.
• Both neutrophils and eosinophils contain specific granules,
the granules contain various enzymes which are released
under certain circumstances.
Eosinophil
 Mediator Cells
• Influence the immune response by releasing various
chemical substances into the circulation.
• Have a variety of biological functions
– Increase vascular permeability
– Contract smooth muscle
– Enhance the inflammatory response
• Two types
– basophils/mast cells
– Platelets
 Basophils

• Basophils easily identified due to large numbers of bluish-

black granules in the cytoplasm.
• The granules are a source of mediators such as histamine
(vasoactive amine that contracts smooth muscle) and
heparin.
• Basophils and platelets are found in the circulation, mast cells
are situated in the tissues of skin, lung and GI tract.
• Bind IgE, a type of antibody formed during allergic reactions.
• Circulating basophils greatly resemble tissue mast cells and it
is likely that they are closely related in function.
• Basophils exist on a few hours in bloodstream.
• Both of these cells play a role in hypersensitivity (allergic)
reactions
Basophil
 Mast cells
• Resemble basophils
• Fixed in the tissues they are connective tissue
cells
• Widely distributed through out the body
• Long life span, 9-18 months
• Plays a role in hypersensitivity reactions by
binding IgE
 Platelets
• Small non-nucleated cells derived from
megakaryocytes of the bone marrow.
• Important in blood clotting.
• Contribute to the immunological tissue injury
occurring in certain types of hypersensitivity
reactions by releasing histamine and related
substances which are contained within
specialized granules in their cytoplasm.
Megakaryocyte & Platelets
 Dendritic Cells
• Primary function is phagocytosis.
• Process antigen material and present it on the
surface to other cells of the immune system,
function as antigen-presenting cells.
• Act as messengers between the innate and
adaptive immunity.
• Classified according to tissue location.
• Found on skin and all major organs.
 Soluble Factors
• Many soluble tissue and serum substances help to suppress
the grow of or kill microorganisms.
• Interferons - family of proteins which are important non-
specific defense mechanisms against viral infections.
• Transferrin - Bacteria do not thrive well in serum that contains
low levels of iron but high levels of transferrin.
• Complement - a group of proteins that are essential for
bacterial destruction and plays an important role in both non-
specific and specific immune mechanisms.
 Acute Phase Reactants (Proteins)
• Defined-normal serum constituents that increase rapidly
because of infection, injury, or trauma to tissues.
• Acute-phase proteins are a class of proteins whose plasma
concentrations increase or decrease in response to
inflammation.
• This response is called the acute-phase reaction .
• In response to injury local inflammatory cells (neutrophils,
granulocytes and macrophages) secrete a number of
cytokines into the bloodstream, most notable of which are
the interleukins.
• The liver responds by producing a large number of acute-
phase reactants.
 C-Reactive Protein
• Increases rapidly within 4-6 hours of infection
or injury.
• Returns to normal rapidly once condition
subsides.
• Used to monitor healing and has also
increased in usefulness in diagnosing
Myocardial Infarction.
 Serum Amyloid A
• Major protein secreted during the acute phase
of inflammation.
• Has several roles, including
– Removes cholesterol from cholesterol-filled
macrophages at site of injury – clean up.
– recruitment of immune cells to inflammatory
sites, and
– Thought to play a role in cholesterol metabolism
 Complement
• A series of serum proteins involved in
mediation of inflammation but also involved
in
– opsonization,
– chemotaxis, and
– cell lysis.
 Alpha-1 Antitrypsin
• Increases during acute inflammation.
• Protects tissues from enzymes of inflammatory cells,
especially elastase.
• When the lungs do not have enough alpha-1
antitrypsin, elastase is free to destroy lung tissue.
• As a result, the lungs lose some of their ability to
expand and contract (elasticity). This leads to
emphysema and sometimes makes breathing
difficult.
 Haptoglobin
• Binds irreversibly to free hemoglobin to
protect kidneys from damage and prevent loss
of iron by urinary excretion.
• Haptoglobin - hemoglobin complex removed
by RES, mainly spleen.
• Used to monitor hemolysis
 Fibrinogen
• A coagulation factor integral to clot formation
which serves as a barrier to prevent spread of
microorganisms further in the body.
• Levels increase with tissue inflammation or
tissue destruction.
• Thought to play a key role in the inflammatory
response and development of rheumatoid
arthritis.
 Immune system divisions

• Innate immunity
– First line of defense
• Adaptive (acquired) immunity
– Takes time to develop
• Humoral immunity
(antibody–mediated specific
immunity)
• Cell-mediated immunity (The
aspect of the adaptive
immune response where
antigen-specific T cell have a
main role)
 Innate vs. adaptive immunity

• Innate immunity
– First line of defense (present in all individuals at all times)
– Immediate (0 – 4 hours)
– Non-specific
– Does not generate lasting protective immunity

• Adaptive immune response (late: > 96 hours)

– Is initiated if innate immune response is not adequate (> 4
days)
– Antigen-specific immunity
– Generates lasting protective immunity (e.g. Antibodies,
memory T-cells)
 Immune system cells
• Adaptive immunity
• Innate immunity
– Lymphocyte
– Granulocytes
(i.e. neutrophils) • B cells
– Macrophages • T cells
– Cytotoxic T cells (CTLs)
– Dendritic cells – Helper T cells (Th)

– Natural killer (NK) cells • Memory cells

 Adaptive immunity

Adaptive immunity:
The form of immunity that is mediated by T or B
lymphocytes and stimulated by exposure to
infectious agents.
 Take effects after innate immune response
 Be the second line of defense against infection
 Characteristics

 Specificity
 Acquired (set up after birth )
 Immune memory
(Adaptive immunity can be enhanced by the second
stimulation of the same antigen)
 Transferable
 Self-limitation
 Composition

T cell : Cell-mediated immunity (CMI)

B cell : Humoral immunity(HI) or antibody-
mediated immunity
 Lymphocytes

• Many types; important in

both humoral and cell-
mediated immunity
• B-cells produce antibodies
(APC cell)
• T- cells
– Cytotoxic T cells
– Helper T cells
• Memory cells
 The process of immune response
in adaptive immunity

Recognition of antigens
Activation,proliferation and differenciation of
T or B lymphocytes
Effector phase of immune response
----Elimination of antigens
Antibodies

• Y-shaped protein molecule.

• Made up of variable and
constant regions.
• Made up of Heavy and Light
chains.
• Produced by B-Lymphocytes
• Function: Recognize
antigens, bind to and
deactivate them.
– Note: Variable region
recognizes the anitgens.
 How an antibody operates/works?

Deactivation of a bacterium by an antibody.

 The Pathway of Specific Immune Response
Step 1
Pathogens eaten by Macrophage

Step 2
Displays portion of Pathogen
on surface

Step 3

Pathogens

Helper-T cell recognizes

Pathogen
Activates Cytotoxic Activates B- Cell

T- Cell

Memory B-Cell
Memory T-Cell

Antibodies
Kills Infected Cells
 Humoral Immunity
• Results in production of proteins called
“immunoglobulins” or “antibodies”.
• Body exposed to “foreign” material termed
“antigen” which may be harmful to body:
virus, bacteria, etc.
• Antigen has bypassed other protective
mechanisms, ie, first and second line of
defense.
 Humoral immune response
V region; At binding
• Cell-surface immunoglobulin
receptors (BCR) detect
extracellular pathogens Fc region
– Once activated, secrete
immunoglobulins as soluble
antibodies
• Antibodies
– Variable region (2 identical
antigen-binding sites)
– Constant region (determines how
antibody disposes of the pathogen
once it is bound)
Mechanisms of Antibody Action

Figure 21.13
 Importance of Humoral Response

• Soluble antibodies
– The simplest ammunition of the immune response
– Interact in extracellular environments such as
body secretions, tissue fluid, blood, and lymph
The Humoral Immune Response (HIR) is the aspect of
immunity that is mediated by secreted antibodies (as
opposed to cell-mediated immunity which involves T
lymphocytes) produced in the cells of the B lymphocyte
lineage (B cell). Secreted antibodies bind to antigens on the
surfaces of invading microbes (such as viruses or bacteria),
which flags them for destruction.[1] Humoral immunity is
called as such, because it involves substances found in the
humours, or body fluids.
 Cell-Mediated Immune Response

• Since antibodies are useless against intracellular

antigens, cell-mediated immunity is needed
• Two major populations of T cells mediate cellular
immunity
– CD4 cells (T4 cells) are primarily helper T cells (TH)
– CD8 cells (T8 cells) are cytotoxic T cells (TC) that destroy
cells harboring foreign antigens
• Other types of T cells are:
– Suppressor T cells (TS)
– Memory T cells
Major Types of T Cells

Figure 21.14
 Importance of Cellular Response

• T cells recognize and respond only to

processed fragments of antigen displayed on
the surface of body cells
• T cells are best suited for cell-to-cell
interactions, and target:
– Cells infected with viruses, bacteria, or
intracellular parasites
– Abnormal or cancerous cells
– Cells of infused or transplanted foreign tissue
T Cell Activation: Step One – Antigen Binding

Figure 21.16
Thank You