Objectives

After working through this module, you should be able to: Explain the mechanisms involved in cellular immunity. Explain the interaction between the components of the immune system in regulating immune response. Describe the mechanism of immune response towards superantigen

Cellular Immune Response

While humoral immune response is for extracellular bacterial, cellular immune response is more for intracellular bacteria, viruses, tumours and transplants. Cells involved in specific cellular immune response are the T lymphocytes

Lymphocyte Activation
Macrophage Il-12, TNF- IFN- NK cell

IL-12 IFN-

IFN-
TH1

TH2

Cross-regulation
Il-4, IL-10 IL-4 IL-5 IL-6 IL-10 IL-13

IL-2 IFN- TNF-

Promotes cellular immunity

Promotes humoral immunity

Antigen Elimination
The elimination of antigens in the effector phase of specific immune responses occurs by the cooperative actions of differentiated lymphocytes and defence mechanisms of innate immunity

In cell-mediated immunity, activated T lymphocytes secrete cytokines, which enhance the functions of phagocytes and other inflammatory leukocytes
However, cytotoxic T cells do not require other cooperating mechanisms to eradicate microbes

Antigen Elimination
Cellular Immunity
MHC-II

Microbe (bacteria) surviving in phagocyte

CD4 recognizes exogenous antigen

MHC-I

Activation of microbicidal functions of phagocyte

Microbe (virus) infecting non-phagocytic cell

CD8 recognizes endogenous antigen

Lysis of infected cell

Regulation of Immune Response

The immune response has to be regulated and

brought back to the normal status as excessive response will be detrimental to the body.

Immunoregulation
Antigen Feedback inhibition IL-1 IL-1 Stimulation

Suppresor T cell

Macrophage

Helper T cell
IL-2

Y Y Y Y Y Y

B cell

Idiotype network interactions

Regulation of Immune Response

Based on the diagram above, the mechanisms of immunoregulation. 1.Control by antigen

level of exogenous antigen intensity of response

2.Feedback control by antibody

IgG inhibit responses via Fc receptor on B-cells

Regulation of Immune Response

3. T-cell regulation

a. activated T-cells express Fas and FasL which restrain unlimited clonal expansion Fas-mediated apoptosis of activated mature cells
b. mutual inhibition between TH1 and TH2 cells suppression

Regulation of Immune Response

4. Idiotype networks antigen-specific receptors on lymphocytes can interact with the idiotypes on the receptors of other lymphocytes to form a network (Jerne)
5. Genetic factors 10 genes control overall antibody response affecting - macrophage ag processing - microbicidal activity - rate of proliferation of differentiating B-cells

Regulation of Immune Response

6. Immunoneuroendocrine networks - interaction among immunologic, neurologic and endocrinologic systems - regulatory interdependent circuits feedback by cytokines augmenting production of corticosteroids shuts down TH1 and macrophage activity - estrogens largely responsible for the more active responses in females relative to males

Regulation of Immune Response

7. Effects of diet and other factors on immunity - protein-calorie malnutrition impairs - exercise - trauma - age: IL-2, TNF, IL-1, IL-6 - environmental pollution

 SUPERANTIGEN
ACTIVITY 1 Based on the diagrams below, how is superantigen different from normal antigen in antigen recognition and stimulating an immune response?

lymphocyte

lymphocyte

TCR
V V Antigen piece V MHC II

TCR

V antigen

MHC II

macrophage
macrophage

ANTIGEN

SUPERANTIGEN

References
Stites DP, Terr Al and Parslow TG. Medical Immunology. 10th Edition,

Appleton & Lange, Prentice-hall International Inc. 2001.

Roitt I, Brostoff J and Male D. Immunology. 6th Edition, Gower

Medical Publishing, London. 2001

Geo.F.Brooks, Janet S.Butel and Stephen A.Morse. Jawetz, Melnick,

& Adelbergs Medical Microbiology. 23rd Edition, McGraw-Hill. 2004.

Cedric Mims, Hazel M. Dockrell, Richard V.Goering, Ivan Roitt, Derek

Wakelin and Mark Zuckerman. Medical Microbiology. 3rd Edition, Elsevier Mosby. 2004.
Marjorie Kelly Cowan and Kathleen Park Talaro. Microbiology A

Systems Approach. McGraw-Hill. 2006.