BASIC CONCEPTS IN IMMUNOLOGY

The perfect world

The real world

IMMUNOLOGY KEYS
Immunity: resistance to disease

Immune
Immune

System: the collection of cells, tissues Response:

and molecules that mediate the resistance

the response made by host to defend itself against foreign substances The coordinated work of these cells and molecules

The

Physiological Function: prevent

and eradicate

DEFENCE AGAINST INFECTION

A. B. C.

Physical barriers Innate immunity Adaptive immunity

BODY DEFENSE
A. Physical barriers (mechanical, chemical & microbial)
1. 2.

quick healing if broken Skin

5.

In-hostile environment

Fatty acid on the skin

3.
4.

Tight epithelial junction Self cleaning

Coughing sneezing Mucous & air flow in the RT Urine flow in the UT Diarrhea and vomiting Saliva, sweat & tears

PH (stomach and urine) Anti-microbial peptides Defensins by epithelial cells Cryptidins by intestinal epithelial cells Surfactant factors in the RT The presence of normal flora Competetion Secretion of antibacterial substances (Colicins) Enzymes lysozymes

BODY DEFENSES
B.

Innate immunity

Consist of chemical and cellular defense mechanism First line of defense Lacks the ability to recognize certain pathogens Lacks the ability to provide specific protective immunity that prevents re-infection (no memory) Triggered immediately Focusing of these mechanisms to site of invasion (inflammation) if inflammation does not remove invaders, Adaptive immunity get activated development of immunological memory. Specificity Is generated by clonal selection of lymphocytes (theory- Fig 1) Takes time Strengthen with second exposure primary response vs secondary response (Fig 2)

C.

Acquired (adaptive immunity)

THE PRINCIPLE MECHANISMS OF

INNATE AND ADAPTIVE IMMUNITY

MECHANISMS OF ADAPTIVE IMMUNITY

CLONAL SELECTION THEORY - FIGURE 1

HISTORY
Early

human societies

Outbreaks
many died survivals remain healthy on subsequent outbreaks

Smallpox

Variola major ~40-80% mortality Variola minor 5-10% mortality

Rinderpest

(cattle plaque) Jenner-1798 used cowpox or vaccinia ---1979 eradicated - Fig 3 Cowpox and canine distemper (failed)

BY

1979 WHO DECLARED SMALLPOX ERADICATED (FIG 3)

HISTORY
Pasteur-1880s vaccine against Fowl cholera in chickens (Pasteurella multocida) Old culture protect accidentally allowed to age Birds remain healthy Second infection with fresh P. multocida no disease Virulent vs avirulent Anthrax & rabies vaccine Salmon

in the USA also dead organism could be

used as a vaccine Robert Koch: infectious disease caused by microorganism (pathogens) each responsible for a particular disease (pathology)

HISTORY

Serum can neutralize toxins and can protect

Antibodies Tetanus toxin is antigen.

THE COURSE OF A TYPICAL ADAPTIVE IMMUNE

RESPONSE

- FIGURE 2

Lag phase 2

Important principle of Humoral immunity

After single injection no Ab is detectable for several days Lag period.
Ab first detectable about one week post injection, and climbs for 10-14 days before declining again and disappeared within few weeks primary response. Second dose injection, 2 days lag period. Faster response, high level of Ab, and more prolonged protection up to months or years. memory cells. Third dose response?? Negative response????

IMPORTANT PRINCIPLE OF CELLMEDIATED IMMUNITY

Destruction and removal of abnormal cells, cancer cells, virus infected cells, and graft rejection. First-set reaction: 7-10 days. Second-set reaction: 1-2 days, and more powerful. Lymphocye.

TERMS
Immune response Antibody Antigen Antigenicity Immunogenicity Antigenic determinant (Epitopes) Haptens Opsonization Antigen presentation Phagocytosis

IMMUNOLOGY KEYS

Immune response: the response made by host to defend itself

against foreign substances

Tolerance: immune system able to recognize its own cell as not foreign, and not elicit immune response Antibody
is a protein that binds specifically to a substance (antigen) all antibodies have the same basic structure produced by cells known as plasma cells binds to and neutralizes foreign substances (pathogens) and prepare them to be engulfed

Phagocytosis : Active process rounded a particle matter

(internalization) by cells - usually referred to as phagocytic cells (phagocytes)

Haptens: small molecule<1000Da not immunogenic and attached to

carrier to induce immune response e.g. penicillin and albumin.

IMMUNOLOGY KEYS
Opsonization: alteration of the surface of a pathogen or other particles so that it can be ingested by phagocytes Antigen:

any molecule that can bind specifically to antibody. not all antigens can generate antibody those antigen that can generate antibody are immunogens.

called

Antigenic determinant: a portion of an antigen that is bound to a given antibody (also called epitope). Antigen presentation: describes the process by which the antigen displayed as a peptide fragments bound to a molecule known as MHC Major histocompatibility complex found on the surface of a cell.

ANTIGENICITY VS IMMUNOGENICITY

Antigenicity: the ability of molecule to be recognized by a product of immune system.

Size, complexity, stability, degradability, and foreignness.

Immunogenicity: the ability of molecule to elicit an immune response. Antigenicity, foreignness Plastic and Stainless steel??

Lipid and nucleic acids are a poor antigenic

Simplicity, instability, rapidly degenerated, Act as Haptens.

Bacterial antigens:
Cell wall: enodtoxin Capsule: K antigen Pili: Flagella: flagellin protein, H antigen Exotoxin: secreated by bacteria.

DETERMINANTS RECOGNIZED BY THE INNATE IMMUNE SYSTEM

Adaptive Immune System Discrete Determinants ()

Reacts with a specific pathogen

Innate Immune System Broad Molecular Patterns

Reacts with a variety of pathogens

DETERMINANTS RECOGNIZED BY THE INNATE IMMUNE SYSTEM

PAMPs Pathogen Associated Molecular Patterns PRRs Pattern Recognition Receptors

PAMP

PRR

Microbial cell wall Complement components Mannosecontaining carbohydrates Polyanions Lipoproteins of Gram + bacteria Yeast cell wall components Mannose-binding protein Scavenger receptors TLR-2 (Toll-like receptor 2)

Biological Consequence of Interaction Opsonization; Complement activation Opsonization; Complement activation Phagocytosis Macrophage activation; Secretion of inflammatory cytokines

CpG islands or CG islands (CGI) are genomic regions that contain a high frequency of CpG sites. The "p" in CpG refers to the phosphodiester bond between the cytosine and the guanine

PAMP
Viral double stranded RNA

PRR
TLR-3

LPS TLR-4 (lipopolysaccharide of Gram bacteria

Flagellin (bacterial TLR-5 flagella)

Biological Consequence of Interaction Production of interferon (antiviral) Macrophage activation; Secretion of inflammatory cytokines Macrophage activation; Secretion of inflammatory cytokines

PAMP

PRR

Biological Consequence of Interaction Production of interferon (antiviral)

U-rich single TLR-7 stranded viral RNA

CpG containing DNA

TLR-9

Macrophage activation; Secretion of inflammatory cytokines

CpG islands or CG islands (CGI) are genomic regions that contain a high frequency of CpG sites. The "p" in CpG refers to the phosphodiester bond between the cytosine and the guanine

Viral antigens:

Cell-Surface antigens:

Blood group Ag: A, B. O, Histocompatibility Ag:MHC1, MHC2

The major histocompatibility complex (MHC) is a set of cell surface molecules encoded by a large gene family in all vertebrates. MHC molecules mediate interactions of

leukocytes, with other leukocytes or body cells.

Clusters of Differentiation: CD4, CD8, .

Cross Reactivity

Cross reactions
Anti-A Ab Anti-A Ab Anti-A Ab

Ag A

Ag B

Ag C

Shared epitope

Similar epitope