This document summarizes cellular immune response (CMI) mediated by sensitized T cells. It describes how CMI is induced through antigen presentation and T cell receptor binding, leading to T cell proliferation and differentiation. The two main effector mechanisms of CMI are the release of cytokines like interleukin-2 and tumor necrosis factor, and the generation of cytotoxic T cells. Cytokines regulate immune cells and have various metabolic and inflammatory effects. Cytotoxic T cells directly kill target cells like virus-infected cells. Tests to detect CMI include skin tests and lymphocyte transformation assays in vitro. CMI plays an important role in immunity against intracellular pathogens and transplants.

1. CELLULAR IMMUNE
RESPONSE
Dr Vishal Kulkarni

2. Introduction-
• Cellular immune response (CMI) is a specific immune
response mediated by sensitized T cells independent
of Abs.
• It was 1st observed by Jenner(1798) & later described
by Koch(1890).
• Delayed hypersensitivity- appearance of skin lesion
48-72 hrs after administration of Ag
• DH & CMI are mediated by T lymphocytes.

3. Induction of CMI-
• Ag is presented by macrophage or react directly.
• Binding of Ag with T cell receptors.
• Proliferation & sequence of morphological &
biochemical events occurs.
• Blast transformation, clonal proliferation,
differentiation occurs.
• Generation of –
• Th & Ts cells
• Cytotoxic T cells
• Lymphokines producing T cells
• Memory cells

4. Proliferated T cells
provides 2 major
effector mechanisms
of CMI
Release of
biologically active
soluble factors
called lymphokines
Generation of
Cytotoxic T cells

5. Cytokines-
Lymphokines- released by activated T lymphocytes.
are regulatory proteins.( mole wt20000-80000)
Monokines- produced by monocytes & macrophages.
Interleukins- product of leucocytes which exert
regulatory influence on other cells.
The lymphokines, monokines, interferons, growth
factors etc. have similer biological effects. Therefore
they are grouped as Cytokines .

6. 1)Cytokines affecting lymphocytes-
 IL-1- is a polypeptide-monokine released by macrophage &
other Ag presenting cells
-Occurs in 2 forms- alpha & beta with same function
-production is stimulated by Ags, toxins, injury, inflamm. Processes.
-inhibited by cyclosporin-A, corticosteroids & prostaglandins.
Immunological effects-
-stimulates activation of Th cells for prod. of IL-2
-stimulate B-cell proliferation & Ab synthesis.
-Stimulate granulocytes & phagocytosis
-mediates various metabolic, physiological, inflammatory&
haematological effects by acting on various types of cells.
-is an endogenous pyrogen.
-with TNF, induces haematologic changes in septic shock.
-has beneficial effects in severe infections in immunocompromised hosts..

7.  IL-2(TCGF)-
-Produced by activated T cells
-is a powerful modulater of the immune response.
-promotes growth & differentiation of T & B cells.
-stimulates cytotoxic T cells & NK cells.
-Convert large granular lymphocytes into LAK cells which can
destroy NK resistant tumor cells.
-this property can be used in T/t of certain types of cancers.

9.  IL-3( Multi CSF)-
-Produced by T cells.
-growth factor for bone marrow stem cells.
-Stimutates multilineage haematopoesis.
 IL-4(B Cell differntiating factor)-
-produced by Th cells
-activates resting B cell.
-enhances activity of cytotoxic T cells.
-increases synthesis of IgG & IgE & may play role in atopic
hypersensitivity.

10.  IL-5
-causes proliferation of activated B cells & eosinophils.
-stimulate production of IgA & IgM
 IL-6
-produced by stimulated T & B cells, macrophages & fibroblasts.
-promotes terminal differentiation of B cells into Ab producing
plasma cells & increases IgG production.
-has stimulatory effect on hepatocytes, nerve cells, &
haematopoetic cells.

11. • Mitogenic/Blastogenic factor-
-released by sensitized T cells stimulated by specific Ag.
-induces nonspecific blast transformation of normal unsensitized
T lymphocytes.
-is imp. in augmenting or amplifying cell mediated immune
response by recruiting uncommited lymphocytes.

12.  Transfer factor-
-An extract from specific Ag sensitized lymphocytes that mediates
passive transfer of CMI is k/a transfer factor.
-both dialyzable & nondialyzable transfer factors have been
identified.
-dialyzable one has LMW(2000-4000)
-Is resistant to treatment with DNAse, RNAse, trypsin, freeze
thawing.
-chemically is a polypeptide-polynucleotide.
-it is immunologically specific.
-highly potent

13. Applications-
• Useful in immunocompromised pts with—
• T cell deficiencies (Wiscott-Aldrich syndrome, Nezelot synd.,
DiGeorge synd.)
• Disseminated infections a/w deficient CMI (TB, Lepromatous
leprosy, Mucocutaneous Candidiasis)
• Cancers (Melanoma, Sarcoma)

14. 2)Cytokines affecting Macrophages-
 Macrophage chemotactic factor-
 Chemotactic for mononuclear phagocytes.
 Causes accumulation of these cells at Ag mediated lymphokine
release.
 Migration inhibition factor-
 Inhibits migration of phagocytic cells & localizes them at the site
of infection.
 Interferons-
 Identified as antiviral agents
 3 types-alpha(leucocytes), beta(fibroblast), gamma(act. T cells)
 IFN gamma causes macrophage activation, neutrophil
augmentation & has antitumor activity.

15. 3)Cytotoxic Lymphokines-
Lymphotoxin-
-released by CTLs cells.
-also k/a TNF-B
-Cytotoxic for tumor cells, transplanted cells & microorganisms.
Tumor necrosis factor alpha-
-causes lysis of tumor cells.
-elimination of certain bacteria & parasites.
-also k/a ‘cachectin’ causing cachexia– a wasting syndrome
during chronic infection because of pronounced catabolic effects.

20. Cytotoxic T cells(CD-8T cells)-
• Capable of killing target cells to which they bind.
• Formed in response to viral infection & graft
from dissimilar member.
• Are cytotoxic to host cells infected with virus;
graft tissues ;tumor cells.
• Mech. Of action-
• Binding of effector cell to target cells through
specific receptors.(ca+ independent stage)
• Changes occurs in target cell which causes lysis.
• Destruction of target cell d/t release of perforins
which puncture target cell

25. Detection of CMI-
In vivo- Skin Test
In vitro-
1.Lymphocyte Transformation Test
2.Target Cell Destruction
3.Migration inhibiting factor test-
-most commonly used test
-macrophages packed in capillary tube are placed in tissue
culture medium in a chamber.
-macrophages migrate out & form lacy fan like appearance
over the glass wall.

26. • If macrophages are from sensitized guinae pig, addition of Ag to
the culture chamber inhibits migration.
• Clinical use- human leucocytes- Ag interaction test.

27. Scope of CMI- plays important role in
-immunity against infectious diseases caused by obligate & facultative
intracellular pathogens.
-delayed hypersensitivity.
-transplantation immunity & graft vs. host reaction.
-Immunological surviellance & immunity against cancer (tumor
rejection)
-Pathogenesis of certain autoimmune diseases e.g. Thyroiditis,
encephalomyelitis.

28. Thank
you.!