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STB 2153

LEARNING UNIT 3:
MECHANISM OF IMMUNITY
Cell-mediated Immunity
Types of Immunity

Natural Acquired

Immune response ready to Immune response developed as


restrict infection a result of infection
• Present at birth • Learned through experience
• Do not provide immunity • Immunity specific for the same
to same pathogens antigens developed
• No different between first • Second exposure stronger
and second exposure than first exposure
• Do not involve memory • Involve memory
Cell-Mediated Immunity
• Cell-mediated immunity involves the production
of cytotoxic T-lymphocytes, activated
macrophages (APC), and cytokines in response
to an antigen and is mediated by T-lymphocytes

• Not involve antibody

• Due to direct action of T-cells


T Lymphocytes
Three major Functions in Immune
Response
Destroy infected cell
(intracellular pathogens)
Maintain Inflammatory response
Regulate both humoral and cellular immnune
reponse
Ontogeny of T-cells
• Processes In T-Cells development
• Production
• Proliferation
• Differentiation & Maturation
Migration:
Figure 5-1 First and Second Phases
Homing
• The movement of naive T-cells into the secondary
lymphoid tissues

• Determined by interaction betweenL-selectin


on the surface of T-cell and two vascular
addressins CD34 and GlyCAM-1 on the surface
of the endothelial cells.
Figure 6-6
Antigen Recognition by T-cells
• T-Cell receptor (TCR)

• TCR have much in common with immunoglobulins; structure, highly


variable and diverse in their antigen specificity.

• Involve clonal distribution like B cell.

• TCR recognize & bind to antigen presented to the them

• TCR attached with CD3 protein to form CD3 complex.


Major Histocampitibily Complex
• TCR recognized peptide antigen that are presented by
MHC molecules.

• The peptide antigen processing and presentation


involve:
1) degradation of pathogen-derived protein into peptide.
2) Peptide assemble into MHC molecules.
3) Display of peptide at the cell surface by MHC molecules
(antigen presentation)
Antigen Recognition by T-cells
• TCR consists of two different
polypeptide chain:
1) TCRα
2) TCRβ

• TCR organized into Variable region


(V regions) and Constant region (C
regions)

• The antigen-recognition site of TCR


is formed Vα and Vβ domain.
TCR & Antibody
T-cell Activation

1) Through reaction with APC

2) Identification of foreign Ag through TCR

3) Cell signalling involve through production of


cytokine

4) Destruction of foreign particle by effector


cell
T-Cell activation

1) Through Reaction With APC

(antigen presenting cells eg. Macrophage, B-cell


& dendritic cell)

 APC will processed the antigen from the pathogen


macromolecule

 APC exhibit the Ag on the MHC molecules


T-Cell activation

2) Identification Of Foreign Ag Through


T-cell Receptor (TCR)

 TCR ONLY recognized Ag on MHC molecule


Major Histocompatibility complex
• MHC Class I

- Present the antigen from pathogen that


replicate intracellularly eg. protein & antigen from
bacteria & viruses
- present peptide to Cytotoxic T-cell (CD8).

• MHC Class II

-Present peptide obtained from pathogen


and their product extracellularly and
have been taken up into the endocytic vesicle of phagocytic cells
-present peptide to helper T-cell (CD4)
Antigen presentation to T-helper cell &
cytotoxic T-cell by MHC molecules
3) Cell Signalling Involve Through Production Of Cytokine

The effector T-cell produce sets of Effector Molecules due to interaction with APC
4) Destruction Of Foreign Particle By Effector Cell
4) Destruction Of Foreign Particle By Effector Cell
Cell mediated Cytotoxicity
• Apoptosis
Action of effector T-cell
• Effector T-cell functions are performed by cytokines & cytotoxins
(Effector Molecules)
Cytokine/cytotoxin Functions
molecules
Tumor Necrosis factor Induce apoptosis, kills chronically infected macrophage
(TNF), Fas ligand
Interferon gamma (IFN), Stimulate/activate macrophage & increase expression of
CD40 ligand MHC II to destroy engulfed microbes

Interleukin 2 (IL-2) Induces T-cell proliferation, increasing the number of


effector T-cell
Interleukin 3 (IL-3) Myelopoiesis – induces macrophage differentiation in
bone marrow
Perforin/granzyme Make pores on target cell membrane, leads to activation
of other nucleases and other enzyme that initiate
apoptosis
Granulocyte-macrophage GM-CSF stimulates stem cells to produce
colony-stimulating factor granulocytes and monocytes.
(GM-CSF),
Killing of virus-infected cell by effector T-
cell by releasing of perforin

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