Ab formation

Immune Elimination Phase Amount of Circulating Ag (%) Fate of the Immunogen Clearance after 1o exposure Equilibrium phase Catabolic decay phase Immune elimination phase Immune Elimination Phase Days after Injection 2 4 6 8 12 10 Amount of Circulating Ag (%) 25 75 100 50 Equilibrium Phase Catabolic Decay Phase Clearance after 2o exposure More rapid onset of immune elimination phase

Kinetics of the Ab Response T-dependent Ag; 1o Response D a y s A f t e r I m m u n i z a t i o n A b T i t e r LAG LOG DECLINE PLATEAU Lag phase Log phase Plateau phase Decline phase

Kinetics of the Ab Response T-dependent Ag; 2o Response 1o Ag 2o Ag D a y s A f t e r I m m u n i z a t i o n A b T i t e r Lag phase Log phase Plateau phase Decline phase * Specificity

Kinetics of Ab Response to T-independent Ags 1o Ag 2o Ag D a y s A f t e r I m m u n i z a t i o n A b T i t e r IgM Ab 4 Phases IgM antibody No secondary response

Milestones in immunization 3000BC Evidence of sniffing powdered small pox crust in Egypt 1700AD Introduction of variolation in England and later in the US 2000BC Sniffing of small pox crust in China 1780AD Edward Jenner discovers small pox vaccine 1500BC Turks introduce variolation 1885AD Pasteur discovers rabies attenuated vaccine

Discovery of small pox vaccine Edward Jenner In 1798, Jenner introduced 1st vaccination (vacca: cow) following his experimentation with isolates of cow pox virus from ‘Blossom’. Discovery of small pox vaccine

Modern era of the vaccine 1920s Diphtheria and Tetanus 1960s Mumps measles and rubella virus Sabin polio 1934 Pertussis 1985 Haemophilus 1955 Salk polio 1990s Hepatitis and varicella

Different modes of acquiring immunity Immunization is the means of providing specific protection against most common and damaging pathogens. Specific immunity can be acquired either by passive or by active immunization and both modes of immunization can occur by natural or artificial means (Figure 1).

Passive Immunity Natural Artificial Placental transfer of IgG Antibodies or immunoglobulins Colostral transfer of IgA Immune cells

Passive Immunization disease indication antibody source human, horse diphtheria, tetanus prophylaxis, therapy vericella zoster human immunodeficiencies gas gangrene, botulism, snake bite, scorpion sting horse post-exposure Artificially acquired passive immunity: Immunity is often artificially transferred by injection with gamma‑globulins from other individuals or gamma‑globulin from an immune animal. Passive transfer of immunity with immune globulins or gamma‑globulins is practiced in numerous acute situations of poisoning (insects, reptiles, botulism), infections (tetanus, measles, rabies, etc.) and as a prophylactic measure hypo-gamma-globulinemia). In these situations, gamma‑globulins of human origin are preferable although specific antibodies raised in other species are effective and used in some cases (acute poisoning and tetanus and diphtheria infections. Passive transfer of cell mediated immunity can also be accomplished in certain diseases (cancer, immunodeficiency). The donor cells must be histocompatible. rabies, human post-exposure hypogamma-globulinemia human prophylaxis

Active Immunization Artificial Natural Attenuated organisms killed organisms exposure to sub-clinical infections sub-cellular fragments This refers to immunity produced by the body in consequence of exposure to antigens. Naturally acquired active immunity: Exposure to different pathogens leads to sub-clinical or clinical infections which result in a protective immune response against these pathogens. toxins others

Live Attenuated Vaccines hepatitis A not required in SC polio* not used in std. schedule measles, mumps & rubella yellow fever Military and travelers Varicella zoster children with no history of chicken pox tuberculosis not used in this country

Recommended Childhood Immunization Schedule (2002)

Complement Discovered in 1894 by Bordet It represents lytic activity of fresh serum Its lytic activity destroyed when heated at 56C for 30 min

Complement functions Host benefit: Host detriment: opsonization to enhance phagocytosis phagocyte attraction and activation lysis of bacteria and infected cells regulation of antibody responses clearance of immune complexes clearance of apoptic cells Host detriment: Inflammation, anaphylaxis

Pathways of complement activation CLASSICAL PATHWAY LECTIN PATHWAY ALTERNATINE PATHWAY antibody dependent antibody independent Activation of C3 and generation of C5 convertase activation of C5 LYTIC ATTACK PATHWAY

HYPERSENSITIVITY A damage to host mediated by preexisting immunity to self or foreign antigen

Types of hypersensitivity reactions Type I: anaphylactic or immediate Type II: cytotoxic Type III: Immune complex Type IV: cell mediated or delayed

Anaphylaxis can be fatal Type-I hypersensitivity The common allergy Anaphylaxis can be fatal

Sensitization against allergens B cell TH1 Histamine, tryptase, kininegenase, ECFA Leukotriene-B4, C4, D4, prostaglandin D, PAF Newly synthesized mediators

Type II hypersensitivity role of neutrophils Complement mediated lysis frustrated phagocytosis ADCC

Type II hypersensitivity role of neutrophils B cell TH1 Histamine, tryptase, kininegenase, ECFA Leukotriene-B4, C4, D4, prostaglandin D, PAF Newly synthesized mediators

Type III hypersensitivity Serum sickness mediated by immune complexes

Type III hypersensitivity mechanism

Type III hypersensitivity mechanism

Type III hypersensitivity the role of immune complex size

Type IV hypersensitivity Delayed reaction 36 to 48 hours Characterized by induration and erythema Also known as cell mediated hypersensitivity Tuberculin test is the most common example

Delayed hypersensitivity reactions epidermal: heavy metals, poison ivy, rubber, latex T cells, later macrophages eczema 48-72 hours contact dermatitis antigen and site histology clinical appearance time of reaction type intradermal: tuberculin, lepromin, etc. lymphocytes, monocytes local induration 48-72 hours tuberculin granuloma persistent antigen stimulus, chronic infection M, giant cells, epitheloid cells, fibroblasts hardening 21-28 days

Mechanism of damage in contact hypersensitivity APC TH1 LAK NK preTc Tc

Comparison of hypersensitivity reactions Type-IV Type-III Type-II Type-I characteristic antibody IgE IgG, IgM none antigen Exogenous cell surface cellular soluble response time 15-30 min. Min.-hrs 3-8 hours 48-72 hours or longer appearance Weal & flare Lysis & necrosis Erythema & edema Erythema & induration baso- and eosinophils Ab and complement histology PMN and complement Monocytes & lymphocytes T-cells antibody transfer with TB test, poison ivy, granuloma farmers’ lung, SLE pemphigus, Goodpasture hay fever, asthma examples

Two major types of immunodeficiency diseases Secondary immunodeficiencies immunodeficiency resulting from infections and other diseases immunodeficiency resulting from iatrogenic causes immunodeficiency due to aging or malnutrition Primary immunodeficiency Inherited immunodeficiencies

Immunologic defects caused by HIV infection Cellular abnormalities decrease in CD4 T cells (reversal of CD4/CD8 ratio) Functional abnormalities increased susceptibility to infections particularly intracellular pathogens decrease in cell mediated immunity decrease in the NK cell functions

Primary immunodeficiency diseases Stem cell defect Reticular dysgenesis T and B cell defect severe combined immunodeficiency X-linked IL2 receptor -chain autosomal adenosine deaminase (ADA) purine nucleoside phosphorylase (PNP)