Chapter 2 Immunology

-antigen or immunogen-
Definition:
Antigens are any foreign substances which can stimulate the immune system.

Factors influencing antigenicity or immunogenicity

1- Foreignness:
- For a substance to be antigenic it must be foreign to the body.
- immune system can normally distinguish between body component (self) and foreign substances (non-self)
2- Molecular size:
* Antigen: must be of high molecular weight i.e small molecules as amino acids are usually not antigenic
Hapten
It is a low molecular weight substance which is incapable alone of inducing an immune response.
It become complete antigen when coupled to a carrier protein  induce immune response.
The hapten molecule acts as an antigenic determinant on the carrier molecule.
Example of haptens are chemicals and drugs e.g. skin ointment, sulpha, penicillin, cosmetics and soaps.

3- Chemical nature:
- The most potent antigens are Proteins, some polysaccharides of high molecular weight are antigenic.
- Nucleic acids and lipids are not antigenic, but lipoproteins & lipopolysaccharides are antigenic.
4- Antigenic determinants (epitopes):
- They are specific small parts on the surface of any antigen (surface marker).
- Responsible for stimulation of a specific immune response.
- The number of epitope on molecules varies with the molecular size.
- For example if an antigen has six different epitopes so, it will produce at least six different antibodies
5- Administration:
- Dose amount:
- A state of unresponsiveness (tolerance) can occur with very high or very low doses.
- Dose number:
- Repeated administration of booster doses are required to stimulate a strong immune response.
- Route:
- Parentral routes are preferred than oral routes as they induce strong immune response.
- Adjuvant:
- Non antigenic substance when mixed with Ag it will  immune response to Ag without altering antigenicity
- Adjuvant slow Ag absorption → prolonged stimulation of immune cells.
- E.g. AL(OH)3 used as Alum. Precipitated toxoid Vaccine against Diphtheria.
6- Host genetic factors:
-To the same Ag some individuals are strong responders than others are weak responders.

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Human tissue Antigens (Iso antigens)
●Blood grouping Ag:
- A and B as well as Rh antigens are present on R.B.Cs.
-These are of vital importance in blood transfusion.
●Histocompatibility Antigens:
-These are molecules (6 glycoproteins) on the membrane of nucleated cells:
-They are known as Major Histocompatibility Complex (MHC), or Human Leukocyte Antigens (HLA):
-Individuals vary in their HLA (So, graft rejection due to response of recipient immunity against donor tissue)
-There are 3 major histocompatibility antigens; class I, class II and class III.
- Histocompatibility genes: These antigens are coded by a set of genes on the short arm of chromosome 6.
-These genes occupy four regions A,B,C and D.
-Regions ABC determine the antigenic specificity of class I.
-Region D determine the antigenic specificity of class II.
-Class III involved in the production of complement components.

DP DQ DR C2 B C4-A C4-B B C A
Chromosome 6
Class 2 Class 3 Class 1 Cell surface
involved in the production of
complement components

MHC class II MHC class I

Types HLA- DP, DQ, DR HLA- A,B,C
On Antigen Presenting Cells (APCs)
Site on all nucleated cells
(B cells, macrophage, dendritic, Langerhans)
Complex with Ag on foreign cells
Complex with Ag on APCs
Function (viral infected, tumor….…etc)
To stimulate Th cells
to stimulate Tc cells
Restriction T helper function restricted on it T cytotoxic function restricted on it

●Importance of MHC:
 Ag presentation with MHC restriction.
 Paternity testing and forensic investigation.
 Organ transplantation and graft rejection.
 Certain HLA antigens associated with a particular disease
e.g. HLA-DR4 with rheumatoid arthritis & HLA-B27 with ankylosing spondylitis
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MHC restriction
➢ Th (CD4+) recognize peptide antigens only on the surface of APCs in association with MHC class II
➢ Tc (CD8+) recognize antigens only on the surface of infected & tumor cells in association with MHC class I

Bacterial antigens
● Correspond to different structure of bacterial cells:
1- ( O ) antigen → somatic antigens or cell wall Ag (polysaccharide part of G –ve cell wall).
2- ( H ) antigen → flagellar Ag.
3- ( C or K ) → capsular Ag.
4- ( Vi ) antigen → virulent antigen is present on the cell surface of some bacteria.

N.B: - The antigenic structures of the bacteria are used for its identification and serotyping of bacteria
Viral antigens
● VAP
● ●
Capsid Viral attachment proteins
Protein coat  * antigenic ● ● - Ab against VAP neutralize infection
●
Ag Ab binding
✓ The antigen antibody binding is key & lock that fit exactly to produce the most efficient immunological response
✓ Sometimes, Antigens can combine with poor fit to an antibody which produced against partially related Ag that
shares one or more epitopes.
- in this condition the binding is called cross reactivity,
- in this condition the cross related Ag called heterophils Ags.
B A
- in this condition the cross reacting Ab called heterophils Ab

• Clinical Examples (invivo):

o In rheumatic fever  Antibody to strept. pyogenes (M protein) cross react with cardiac muscle
Laboratory Examples(invitro):
1- Mono spot & Paul Bunnel test:
used in diagnosis of infectious mononucleosis (caused by E.B.V )
- Antibodies in the serum of these patients is heterophile can react with horse or sheep R.B.Cs.

N.B : - All laboratory tests using Heterophile Ag are non specific test for diagnosis (good negative test )

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T-independent Antigens T-dependent Antigens

e.g. capsular polysaccharide, consist of repeated subunits of
several sugars that cross link the IgM antigen receptor on the
B cells and activate it in absence of Th cells
Stimulate IgM responses i.e always primary
Fail to generate memory cells
e.g. protein in nature
here B cells act as antigen presenting cells
with the need of Th cell to be activated
Stimulate IgM & IgG responses
Generates memory cells

N.B: The cytokines produced by Th cells are needed for class switch from IgM to IgG or other class of Ig

Super Antigens
Definition: They are antigens capable of activating multiple clones of T helper cells
Character:
-They are active at very low concentration
-They clamp between MHC class II on APCs and B chains of TCR on Th cells outside the binding groove
-They activate multiple clones of T helper cells large amount of cytokines  systemic toxicity
Examples:
➢ Bacterial toxins especially staphylococcal enterotoxins, toxic shock syndrome toxins (TSST)

Classic Ag Steps Super Ag


Ag
Processed Processing Not processed
By macrophage

 Presentation outside
Presentation inside a2 b2 a2 b2
Presentation groove act as a clamp
groove a1 b1 On MHC II a1 b1 cross link MHC with TCR
Super Ag


Bind with Ag
 Bind with
Variable region of Recognition Variable region
both b and a chain By TCR of b chain only
av bv av bv
of TCR  of TCR
ac bc  ac bc Non specific
Specific activation T cell
activation
of T cell Activation
of T cell


Release the required Level of Release very high
benefit level Released harmful level
cytokines

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