1 basic concepts in immunology

7/27/2019 1 Basic Concepts in Immunology

1/31

BASIC CONCEPTSIN IMMUNOLOGY


2/31

The perfect world


3/31

The real world


4/31

IMMUNOLOGYKEYS

Immunity: resistance to disease

Immune System: the collection of cells, tissuesand molecules that mediate the resistance

Immune Response: the response made by host to defend itself against

foreign substances

The coordinated work of these cells and molecules

The Physiological Function: preventand eradicate


5/31


6/31

DEFENCE AGAINST INFECTION

A. Physical barriers

B. Innate immunity

C. Adaptive immunity


7/31

BODYDEFENSE

1. quick healing if broken

2. Skin

Fatty acid on the skin

3. Tight epithelial junction

4. Self cleaning

Coughing sneezing

Mucous & air flow in the

RT

Urine flow in the UT

Diarrhea and vomiting

Saliva, sweat & tears

5. In-hostile environment

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

A. Physical barriers (mechanical, chemical & microbial)


8/31

BODYDEFENSES

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

C. Acquired (adaptive immunity) 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)


9/31

THEPRINCIPLEMECHANISMSOF

INNATEANDADAPTIVEIMMUNITY


10/31

MECHANISMSOFADAPTIVEIMMUNITY


11/31

CLONALSELECTIONTHEORY- FIGURE 1


12/31

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 ---1979eradicated - Fig 3

Cowpox and canine distemper (failed)


13/31

BY 1979 WHO DECLAREDSMALLPOXERADICATED (FIG 3)


14/31

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 USAalso dead organism could be

used as a vaccine

Robert Koch: infectious disease caused bymicroorganism (pathogens) each responsible for aparticular disease (pathology)


15/31

HISTORY

Serum can neutralize toxins and can protect Antibodies

Tetanus toxin is antigen.


16/31

THECOURSEOFATYPICALADAPTIVEIMMUNE

RESPONSE- FIGURE 2

Lag phase 2


17/31

Important principle of Humoral

immunity

After single injection no Ab is detectable for several days Lag

period.

Abfirst detectable about one week post injection, and climbs for

10-14 days before declining again and disappeared within fewweeks 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????


18/31

IMPORTANTPRINCIPLEOF CELL-

MEDIATEDIMMUNITY

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.


19/31

TERMS

Immune responseAntibody

Antigen

Antigenicity

ImmunogenicityAntigenic determinant (Epitopes)

Haptens

Opsonization

Antigen presentation Phagocytosis


20/31

IMMUNOLOGYKEYS

Immune response: the response made by host to defend itselfagainst foreign substances

Tolerance: immune system able to recognize its own cellas 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 themto be engulfed

Phagocytosis : Active process rounded a particle matter(internalization) by cells - usually referred to as phagocytic cells(phagocytes)

Haptens: small molecule


21/31

IMMUNOLOGYKEYS 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 calledimmunogens.

Antigenic determinant: a portion of an antigen that isbound to a given antibody (also called epitope).

Antigen presentation: describes the process by whichthe antigen displayed as a peptide fragments bound to amolecule known as MHC Major histocompatibility complexfound on the surface of a cell.


22/31

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 animmune response.

Antigenicity, foreignness

Plastic and Stainless steel??


23/31

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.


24/31

DETERMINANTS RECOGNIZEDBYTHE

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


25/31

DETERMINANTS RECOGNIZEDBYTHE

INNATE IMMUNE SYSTEM

PAMPs Pathogen Associated Molecular Patterns

PRRs Pattern Recognition Receptors

Biological


26/31

PAMP

PRR

Biological

Consequence of

Interaction

Microbial cell wall

components

Complement Opsonization;

Complement

activation

Mannose-

containing

carbohydrates

Mannose-binding

protein

Opsonization;

Complement

activation

Polyanions Scavenger receptors Phagocytosis

Lipoproteins of

Gram + bacteriaYeast cell wall

components

TLR-2 (Toll-like

receptor 2)

Macrophage

activation;Secretion of

inflammatory

cytokines

CpG islands orCG islands (CGI) are genomic regions that contain a high frequency of CpGsites. The " " in C G refers to the hos hodiester bond between the c tosine and the uanine
http://en.wikipedia.org/wiki/CpG_sitehttp://en.wikipedia.org/wiki/CpG_sitehttp://en.wikipedia.org/wiki/Phosphodiester_bondhttp://en.wikipedia.org/wiki/Cytosinehttp://en.wikipedia.org/wiki/Guaninehttp://en.wikipedia.org/wiki/Guaninehttp://en.wikipedia.org/wiki/Cytosinehttp://en.wikipedia.org/wiki/Phosphodiester_bondhttp://en.wikipedia.org/wiki/Phosphodiester_bondhttp://en.wikipedia.org/wiki/Phosphodiester_bondhttp://en.wikipedia.org/wiki/CpG_sitehttp://en.wikipedia.org/wiki/CpG_sitehttp://en.wikipedia.org/wiki/CpG_site


27/31

PAMP PRR

Biological

Consequence of

Interaction

Viral double

stranded RNA

TLR-3 Production of

interferon

(antiviral)

LPS

(lipopolysaccharideof Grambacteria

TLR-4 Macrophage

activation;Secretion of

inflammatory

cytokines

Flagellin (bacterialflagella)

TLR-5 Macrophageactivation;

Secretion of

inflammatory

cytokines


28/31

PAMP PRR

Biological

Consequence of

Interaction

U-rich single

stranded viral RNA

TLR-7 Production of

interferon

(antiviral)

CpG containing

DNA

TLR-9 Macrophage

activation;

Secretion of

inflammatory

cytokines

CpGoffrequencyhighacontainthatregionsgenomicare(CGI)islandsCGorislandsCpGguaninetheandcytosinethebetweenbondphosphodiesterthetorefersCpGin"p"The.sites
http://en.wikipedia.org/wiki/CpG_sitehttp://en.wikipedia.org/wiki/Guaninehttp://en.wikipedia.org/wiki/Cytosinehttp://en.wikipedia.org/wiki/Phosphodiester_bondhttp://en.wikipedia.org/wiki/Phosphodiester_bondhttp://en.wikipedia.org/wiki/CpG_sitehttp://en.wikipedia.org/wiki/CpG_sitehttp://en.wikipedia.org/wiki/Phosphodiester_bondhttp://en.wikipedia.org/wiki/Phosphodiester_bondhttp://en.wikipedia.org/wiki/Phosphodiester_bondhttp://en.wikipedia.org/wiki/Cytosinehttp://en.wikipedia.org/wiki/Guaninehttp://en.wikipedia.org/wiki/CpG_sitehttp://en.wikipedia.org/wiki/CpG_site


29/31

Viral antigens:


30/31

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, .


31/31

Cross Reactivity

Anti-A

Ab

Ag A

Anti-A

Ab

Ag B

Shared epitope

Anti-A

Ab

Ag C

Similar epitope

Cross reactions

1 basic concepts in immunology

Documents