Immunodeficiency

Infections

Tumors

Hyperactive immune responseSevere allergic reactionsAutoimmunity

Immunity

resistance of an organism to infection, disease, or other unwanted biological invasion

exclusion from legal obligations, such as liabilities and punishments

Antigen

- Proteins / polysaccharides (microbial / nonmicrobial)

- Prompt generation of antibodies (binds to antigen)

- Elicits an immune response (immunogen)

- Exogenous / endogenous / self

Epitope

Immunologically active regions on antigen, that bind to specific

membrane bound receptors on lymphocytes or to secreted

antibodies

Antibody

- Immunoglobulins (gamma globulins) found in blood

and body fluids

- Used by the immune system to identify and bind to

antigens

- Produced by B lymphocytes

- Can belong to 5 classes IgG, IgA, IgM, IgE, IgD

- Specificity is very high

Antibody- They have a basic unit of two light chains (κ and λ) and

two heavy chains (γ, α, μ, δ, ε)

Antibody- Each antibody unit has two antigen binding sites (Fab)

and one Fc

Fab

Fc

Immunoglobulins - Functions

IgG:

- Major component. 70-75% of total immunoglobulin pool

- Serum concentration is about 800-1600 mg/dl

- Distributed evenly in the intra and extra vascular pools

- Major antibody of the secondary (adaptive) immune response

- Can move across placental barrier (passive immunity to new

born)

Immunoglobulins - Functions

IgM:

- 10 % of total immunoglobulin pool. Exists as a pentamer

- Serum concentration is about 50-200 mg/dl

- Largely confined to the intravascular pool

- Rises early in response to infection / immune stimulus

- Cannot move across placental barrier

Immunoglobulins - Functions

IgA:

- 15 - 20 % of total immunoglobulin pool.

- Serum concentration is about 150-400 mg/dl

- Predominant antibody in body secretions (saliva, milk, gastro-

intestinal, urine)

- Exists as a non-secretory (monomer) and secretory (dimer)

- Participates in mucosal immunity

Immunoglobulins - Functions

IgD:

- <1 % of total immunoglobulin pool.

- Biological function unknown

Immunoglobulins - Functions

IgE:

- Very low levels in serum (20-500 ng/ml)

- Higher levels on surface membranes of basophils and mast

cells, and in bronchial and conjunctival mucosa

- Associated with allergic diseases such as asthma and hay

fever, and with immunity to helminthic infestations

Immunity

Innate (natural / native)(less specific)

- Defense mechanisms present even before exposure to Ag.

- Components

- Epithelial barriers

- Phagocytes

- Natural Killer (NK) cells

- Complement (activation through alternate and lectin path)

- Toll Like receptors on phagocytes

- Cytokines

Innate immunity:

- Physical barriers - Skin, mucus membranes

- Inflammatory barriers - Leakage of fluid containing

chemical mediators

- Chemical barriers - Lysozyme, complement, interferon,

toll like receptors

- Phagocyte barriers - Neutrophils, macrophages

- Others - Natural Killer Cells

Natural Killer Cells (Large Granular Lymphocytes)

- 10-15% of peripheral blood lymphocytes

- Have innate ability to kill tumor cells and virus infected cells,

without prior sensitization

- First line of defense against viral infections (? tumors)

- Participates in antibody dependent cell mediated cytotoxicity

Adaptive Immunity (Acquired / Specific) (Immune response)

Varicella zoster

First exposure

RecoveryRecovery

Subsequent exposures

(Vaccination)

Effector response(first exposure)

INFECTING AGENT

IMMUNE REACTION

ANTIGEN DESTRUCTION

Disease

Specific immune response

Specific immune memory

Lasts many yearsRecovery

Specific immune memory

Specific antigen recognition

INFECTING AGENTMemory response(subsequent exposures)

ALMOST IMMEDIATEIMMUNE REACTION

VERY RAPID ANTIGENDESTRUCTION

Rapid activation andamplification ofimmune response

Enhancement ofspecific immune responseNO DISEASE

Adaptive Immunity

(Acquired / Specific) (Immune response)

- T lymphocytes

- B lymphocytes

- Complement (classical pathway)

- Antigen presenting cell

- Cell mediated immunity (against intracellular microbes)

- Antibody mediated immunity (against extracellular microbes and toxins)

Cell mediated immunity:

T lymphocytes:

- Thymus processed. Constitute 60-70% of blood lymphocytes

- Localize in T zones of lymphocytes (para-cortical areas) and peri-

arteriolar sheath of spleen

- Express receptors that recognize MHC antigens

- Can be activated ONLY by processed membrane bound antigens on

antigen presenting cells

- Express molecules on their surface called cluster determinants (CD)

- CD4+ T cells (T helper cells) (60% of mature T cells)

- CD8+ T cells (T suppressor cells) (30% of mature T cells)

CD4+ T helper cells:

- Master regulator of immune response

- Secretes cytokines that influence all other cells of immune system

- Two subsets

THH1 (secretes IL-2 and IFN-ϒ) - facilitates delayed hypersensitivity,

macrophage activation and opsonin synthesis

TH2 (secretes IL-4, IL-13, IL-5) - stimulates IgE synthesis and activation of

eosinophils

CD8+ cells act mainly as cytotoxic cells.

Also secrete cytokines similar to THH1 cells

B Lymphocytes

- Develop from immature precursors in the bone marrow

- Constitute 10-20% of peripheral blood lymphocytes

- In lymph nodes, found in the follicles. In spleen - white pulp

- Express surface immunoglobulins

- Surface IgM is involved in antigen binding

Antigen Presenting Cells (APC / accessory cells)

- Cells capable of internalizing antigen (phagocytosis / endocytosis),

process antigen and re-express it bound to MHC Class II

- Three types of APC

a) Dendritic cells

b) Macrophages

c) B Lymphocytes

Cytokines: (Messenger molecules)

- Chemical messengers that mediate and regulate inflammatory,

reparative and immunologic responses by effector cells.

a) Cytokines that mediate innate immunity:

Interleukin-1 (IL-1), Tumor Necrosis factor (TNF),

Type 1 interferon, IL-6

b) Cytokines that regulate lymphocyte growth, activation and

differentiation (IL-2*, IL-4, IL-12,IL-15, TGF-β).

c) Cytokines that activate inflammatory cells (IFN-γ, IL-5, TNF)

d) Cytokines that affect leukocyte movement (chemokines)

e) Cytokines that stimulate hematopoiesis

Cytokines: (General properties)

- Same cytokine may be produced by many cell types

- Same cytokine may act on many cell types (pleiotropic action)

- Act in 3 ways

a) On the same cell that produces them (autocrine)

b) On the other cells in the vicinity (paracrine)

c) On remote cells systemically (endocrine)

- Mediate effects by binding to specific high affinity receptors

MHC Molecules

- Large genomic region (gene family) found in all vertebrates

- Plays an important role in

Immune system

Autoimmunity

Transplantation

Reproductive success

MHC Molecules

- Antigens of MHC are expressed on the surface of many cells

- Principal function of these is to bind peptide fragments of

foreign proteins for presentation to antigen specific T cells

- Genes are located on chromosome 6

- System is highly polymorphic

- Three categories of MHC genes

Class I and Class II are involved in antigen presentation

Class III encode complement proteins

MHC Molecules

- Role of MHC (HLA) complex:

a) Organ transplantation: recipient’s immune system recognizes

donor organ HLAs and accept / reject it

b) Regulation of immune system:

Class I antigens regulate function of CD8+ cells in viral infections

Class II antigens regulate function of CD4+ cell