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Lecture - Cell Mediated Immunity

Cell-mediated immunity involves T lymphocytes recognizing antigens displayed on the surface of other cells through MHC molecules, leading to T cell activation and responses like delayed type hypersensitivity and cytotoxic killing of infected or tumor cells. CD4+ T cells enhance cell-mediated immunity through cytokine production and activation of other immune cells like macrophages. Cell-mediated immunity provides protection against intracellular pathogens and tumors.

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rockyrawat01012003
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42 views

Lecture - Cell Mediated Immunity

Cell-mediated immunity involves T lymphocytes recognizing antigens displayed on the surface of other cells through MHC molecules, leading to T cell activation and responses like delayed type hypersensitivity and cytotoxic killing of infected or tumor cells. CD4+ T cells enhance cell-mediated immunity through cytokine production and activation of other immune cells like macrophages. Cell-mediated immunity provides protection against intracellular pathogens and tumors.

Uploaded by

rockyrawat01012003
Copyright
© © All Rights Reserved
Available Formats
Download as PDF, TXT or read online on Scribd
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Cell Mediated Immunity

(CMI)
Cell-Mediated Immunity (CMI)

Antigen T-lymphocytes

Immune responses
Cell Mediated Immunity
• Cell-mediated immunity (CMI).

• T cells (lymphocytes) bind to the surface of


other cells (Antigen Presenting Cells) that
display the antigen and trigger a response
Antigen Presenting cells

Monocytes : Peripheral blood


Macrophages : Tissues
Dendritic cells : Lymphoid tissues
Langerhans cells : Epidermis
B-cells : Lymphoid tissue, Blood
Lymphocyte

Macrophage

Lymphocyte
6

1
5

4 2

3
Invariant chain(Ii)
T cell Activation
Antigen Presentation
T cell Activation
Antigen Presentation
CMI

T lymphocytes

Other cells
1. Endogenous antigen

2. Exogenous antigen
Virus

Target cell
Target cell
Target cell
Target cell

Host cell

Transcription
Translation Viral protein
Exogenous antigen
Microbes
Proteins

Cell-mediated immunity
Exogenous antigen
CD4+ T-lymphocytes
(CD4+ cells)

Class II MHC
APC APC

CMI
Antigen presenting cells
Monocytes/Macrophages
Dendritic cells
Langerhans cells
B-cells
6

1
5

4 2

3
Invariant chain(Ii)
TCR-MHC interaction
T cells T cells
T cells

TCR TCR TCR

X X Y
MHC MHC MHC

APC APC APC


Recognition No Recognition
CD4-MHC class II interaction

Antigen presenting cell Antigen presenting cell Antigen presenting cell

CD4 MHC CD4


class CD4
II

TCR

T cell T cell T cell


Cell-Mediated Immunity
• Lymphocytes: (B & T lymphocytes)

• B lymphocytes ("B cells"): These are responsible for


making antibodies (humoral immunity)

• T lymphocytes ("T cells"): CMI


• Subsets include:
– CD8+ cytotoxic T lymphocytes (CTLs) that kill virus-infected
and tumor cells
– CD4+ helper T cells enhance CMI and production of antibodies
by B cells
Cell-Mediated Immunity
• Examples of Cell-Mediated Immunity
• Delayed-Type Hypersensitivity (DTH): the
tuberculin test (or Mantoux test)
• Tuberculosis: a chronic disease, caused by
Mycobacterium tuberculosis
• The response to tuberculin is called "delayed"
because of the time it takes to occur (in contrast to
the "immediate" responses characteristic of many
antibody-mediated sensitivities like an allergic
response to a bee sting).
Cell Mediated Immunity
• DTH is a cell-mediated response
• Anti-tuberculin antibodies are rarely found
in tuberculin-positive people
• The T cells responsible for DTH are
members of the CD4+ subset
Cell-Mediated Immunity
• Contact Sensitivity
• Many people develop rashes on their skin following
contact with certain chemicals such as nickel, certain dyes,
and the active ingredient of the poison ivy plant
• The response takes some 24 hours to occur, and like DTH,
is triggered by CD4+ T cells
• The actual antigen is probably created by the binding of
the chemical to proteins in the skin
• The fragments of antigen are then presented to CD4+ T
cells by phagocytic cells in the skin by antigen presentation
Activation of helper T cells
• Requires recognition of antigen complex on
the surface of antigen-presenting cells eg,
macrophages consisting of both antigen and
class II MHC proteins
• Viral antigens are recognized in association
with class I MHC proteins
• This is called MHC restriction
Cellular Basis of Immune Response
• Two signals are required to activate T cells
• First signal
• Class II MHC + antigen – TCR
– IL-1, LFA-1 with ICAM
• Second signal (Costimulatory signal)
– B7 on APC interacts with CD28 on lymphocyte
T cell Activation
• In the absence of co-stimulatory signal state of
unresponsiveness called “anergy” develops
• Production of co-stimulatory protein depends on
activation of the toll like receptor on antigen
presenting cell
• Foreign antigens such as bacterial proteins induce
B7 protein where as self proteins do not
T cell Activation
• Consequent to antigen recognition by TCR,
signal is transmitted through CD3 molecule
• This results in influx of calcium into the cell
• Calcium activates calcineurin
• Calcineurin activates gene for IL-2 and its
receptor
Out come of T helper cell activation

• Production of IL-2 and its receptor


– IL-2 is also know as T cell growth factor
– Proliferation of antigen specific T cells
– Effector and regulatory cells are produced
along with “memory” cells
– IL-2 also stimulates CD8 cytotoxic cells
Out come of T helper cell activation

• Production of Gamma Interferon (IF)


– It increases expression of Class II MHC
proteins
– It enhances the ability of APC to present
antigen to T cells
– It enhances the microbicidal activity of
macrophages
– Enhances immune response
Out come of T helper cell activation

• Memory T cells
• Respond rapidly for many years after initial
exposure to antigen
• A large number of memory cells are produced so
that the secondary response is greater than the
primary
• Memory cells live for many years and have the
capacity to multiply
• They are activated by smaller amount of antigen
• They produce greater amounts of interleukins
Effector functions of T cells

1. Delayed type of hypersensitivity mediated by


Th-1 type of CD4 positive cells

2. Cytotoxicity: mediated by CD8 +ve cells.


Directed against virus infected cells, tumor
cells and allografts
Killing by cytotoxic cells

– Perforins
– Granzymes – degrading enzymes
– Fas-Fas Ligand interaction - apoptosis
– Antibody dependent cellular cytotoxicity
– Immune surveillance
– Allograft rejection
Killing Mechanisms of Cytotoxic
T cells
Activation of B cells
• B cell functions as APC
• Multivalent antigen binds to surface IgM
• Cross links adjacent Ig molecules
• Igs aggregate to form “patches” and migrate to
one pole to form a cap
• Capped material is endocytosed
• Antigen is processed and epitopes appear on the
cell surface in association with Class II MHC
proteins

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