Antigens & Immunogens

Immunogen
*

A foreign substance, when introduced into host body, stimulate formation of specific antibodies or sensitized lymphocytes

Antigen

* Antigens have the ability to combine specifically with antibodies produced or sensitized T-lymphocytes induced

Haptens
- Low molecular weight substances - These substances not immunogenic by itself - If couple to a larger carrier molecule (albumin, globulins), they become immunogenic - Examples : simple chemicals and drugs: penicillin, sulphonamid, aspirin, cosmetic, tranquillizers, neomycin skin ointment

Epitope or antigenic determinant

Small part of an antigen that interacts with an

antibody Any given antigen may have several epitopes. Each epitope is recognized by a different antibody or TCR

Factors influencing Immunogenicty

1-Foreigness :
Foreign substances are immunogenic

2- Molecular size:
High molecular weight increase immunogenicty

3- Chemical structure complexity:

` High complexity increase immunogenicty Protein - most effective Polysaccharide simple , complex Lipids - poor Nucleic Acids - poor

4- Route of administration:

Factors influencing Immunogenicty

5- Method of administration: a- Antigen dose: Appropriate dose
antigenicty Low dose High dose optimum

low- zone tolerance high-zone tolerance

b- Adjuvant:
Substance when injected with an antigen enhance immunogenicty

T dependent Ag - T cell help to B cells

Signal 2 - T cell help
IL-2 and other cytokines

Signal 1 antigen & antigen receptor

Y YY

Th Th
1. T cell antigen receptor 2. Co-receptor (CD4) 3.CD40 Ligand

T-independent antigens
polysaccharides and proteins with many

identical polypeptides Many bacterial capsules & bacterial flagellar proteins

This stimulates the B cell to generate antibody-

secreting plasma cells without the help of IL-2. While this response is an important defense against many bacteria, it generates a weaker response than T-dependent antigens and generates no memory cells.

Thymus independent antigens

Principal example:

LPS

Principal example(s):

Bacterial capsules Bacterial flagella

Mechanism: extensive cross-linking of mIg

T Dependent & Independent Antigens

T Dependent Antigens Induce responses in athymics Polyclonally activate B cells Require repeating epitopes Affinity maturation Isotype switching Immunological memory No No No Yes Yes Yes TI-1 Antigens Yes Yes No No No No TI-2 Antigens Yes No Yes No Limited No

Innate Immunity
P athogen A ssociated M olecular P atterns PRRs: P attern R ecognition R eceptors
PAMPs:

PAMP

PRR

Innate Immune cells

Direct Bactericidal Activity
Phagocytosis Oxygen burst Anti-microbial peptides

Inflammatory and effector cytokines

Bacterial Structures
Flagella Pili Capsule Plasma Membrane Cytoplasm Cell Wall Lipopolysaccharid

es Teichoic Acids Inclusions Spores

Chapter 4

Macromolecule Proteins

Primary Subunits Where found in cell amino acids Flagella, pili, cell walls, cytoplasmic membranes, ribosomes, cytoplasm sugars (carbohydrates) fatty acids nucleotides capsules, inclusions (storage), cell walls membranes DNA: nucleoid (chromosome), plasmids rRNA: ribosomes; mRNA, tRNA: cytoplasm

Polysaccharides Phospholipids Nucleic Acids (DNA/RNA)

Cytoplasm
Bacterialchromosome(DNA) Ribosomes various sorts ofinclusions
Bacterial CpG DNA: (PuPuCpGPyPy) ISS-DNA

unmethylated, present in expected 1/16 frequency,

CpG in vertebrates

methylated, frequency at around 1/60

TLR 9 Potent Immune response Macrophage activation Cytoplasmic membrane Lipid rich

Cell wall & its associated structures

Capsule Pili and Fimbriae Flagella

Capsule
Polysaccharide Except B. anthracis protein

polymer of D-glutamic acid Phagocytosis protection Anticapsular antibodies protect animal K antigens

Fimbriae attachment & Pili conjugation F antigens Short protein appendages smaller than flagella Adhere bacteria to surfaces
E. coli has numerous types

Fimbriae and Pili

K88, K99, F41, etc.

Antibodies to will block adherance

F-pilus; used in conjugation Exchange of genetic information

Flagella
Flagellin H antigen Motility TLR 5

Cell Wall
Peptido-glycan Polymer (amino acids +

sugars) Unique to bacteria Sugars; NAG & NAM

N-acetylglucosamine N-acetymuramic acid

D form of Amino acids used Hard to break down D form Amino acids cross link NAG & NAM
Chapter 4

Teichoic Acids
Gram + only Glycerol, Phosphates, & Ribitol Attachment for Phages Liptoteichoic acid ion transport

Endotoxin of Gram-negatives
Gramnegative cell cytopl. mem. peptidoglycan outer mem.

Lipopolysaccharide (LPS)

Lipid A
The toxic part

Core polysaccharide
Helps solubilise Lipid A

O sidechain
Somatic antigen

Lipopolysaccharide (LPS)
G- bacteria only Lipid A Polysaccharide O Antigen somatic antigen Appearance of Colonies
Mucoid = Smooth (lots of LPS or capsule) Dry = Rough (little LPS or capsule)

O Ags differ in Sugars, not Lipid A Configuration of Glycosidic linkage O

serotypes

Proteins of Outer membrane

Lipoprotein Outer membrane proteins Outer membrane phospholipids

Lipopeptides Lipoteichoic Acid Unmethylated DNA Oligomers

Peptidoglycan

a- Antigens related to bacterial cells Somatic antigen (O) - cell wall Gm ve bacter. Capsular antigen (K) - usually polysaccharide Flagellar Ag (H) - flagellin Fimbrial Ag (F) Fimbrial protein b- Antigen secreted by bacteria:
- Exotoxins - Enzymes

Other antigens
Porins Heat shock proteins Mycobacteria Trehalose dimycolate (cord

factor) M protein of Streptococci Protein A Staph. Aureus

Fc portion of IgG