Cell mediated immunity cmi
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Cell-Mediated Immunity CMI. Specialized lymphocytes, mostly T cells, respond to intracellular Ags After differentiating in the thymus, T cells migrate to lymphoid tissue T cells differentiate into effector T cells when stimulated by an Ag Some effector T cells become memory cells. T Cells.

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Cell-Mediated Immunity CMI

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Cell mediated immunity cmi

Cell-Mediated ImmunityCMI

  • Specialized lymphocytes, mostly T cells, respond to intracellular Ags

  • After differentiating in the thymus, T cells migrate to lymphoid tissue

  • T cells differentiate into effector T cells when stimulated by an Ag

  • Some effector T cells become memory cells


T cells

T Cells

  • Helper T Cells (CD4, TH)

    • TH1 Activate cells related to cell-mediated immunity

    • TH2 Activate B cells to produce eosinophils, IgM, and IgE

  • Cytotoxic T Cells (CD8, TC)

    • Destroy target cells with perforin


T cells1

T Cells

  • Delayed Hypersensitivity T Cells (TD) (CD4)

    • Associated with allergic reaction, transplant rejection, and tuberculin skin test

  • Suppressor T cells (TS) (CD8)

    • Turn off immune response when Ag no longer present


Structure of t cell receptor

Alphachain

Beta

chain

Variable region “V”

CHO

CHO

CHO

CHO

Constant region “C”

Hinge “H”

Disulfide bridge

+

Transmembrane region

+

+

Cytoplasmic tail

Structure of T Cell Receptor


Structure of t cell receptor tcr

Structure of T Cell Receptor (TCR)

  • Two polypeptide chains, α and β, of roughly equal length

  • Both chains consist of a variable (V) and a constant (C) region

  • α chain V region has a joining (J) segment

  • β chain V region has both a J and diversity (D) segment


Structure of t cell receptor continued

Structure of T Cell Receptor(continued)

  • Hypervariable regions in V contribute to diversity of TCR

  • TCR recognizes portions of MHC molecule and peptide bound in the groove


What does the t cell receptor tcr recognize

What Does the T Cell Receptor (TCR) Recognize?

  • Only fragments of proteins (peptides) associated with MHC molecules on surface of cells

  • Helper T cells (TH) recognize peptide associated with MHC class II molecules

  • Cytotoxic T cells (Tc) recognize peptide associated with MHC class I molecules


Interactions of t h cell and apc

peptide

Interactions of TH Cell and APC

T helper

lymphocyte

TCR

LFA-2

LFA-1

CD28

TNF-alpha

IL-1

IL-6

IL-12

IL-15

TNF-beta

IFN-gamma

GM-CSF

IL-4

CD4

Antigen-

presenting

cell

LFA-3

ICAM-1

B7-1/B7-2

(CD80/CD86

Class II

MHC


Interactions of tc cell and target cell

peptide

Interactions of Tc Cell and Target Cell

T cytotoxic

lymphocyte

TCR

LFA-1

LFA-2

CD8

Target

cell

Class I

MHC

ICAM-1

LFA-3


T independent antigens

T-independent Antigens

B cell

Figure 17.17


T dependent antigens

T-Dependent Antigens

Figure 17.16


T dependent and independent antigens

T-dependent and independent antigens


Self mhc restriction

Self MHC Restriction

  • T cells recognize foreign antigen associated with self MHC

  • No value for individual to have T cells that recognize foreign antigen associated with foreign MHC

  • Self MHC restriction occurs in thymus


Process of self mhc restriction in thymus

Process of Self MHC Restriction in Thymus

  • T cells with TCR recognizing self MHC molecules are retained – “positive selection”

  • Retained T cells with TCR recognizing self peptide associated with self MHC are eliminated – “negative selection”

  • Self MHC-restricted T cells are released


Dendritic cells present antigens

Dendritic cells present antigens

Figure 17.12


Helper t cells

Helper T Cells

Figure 17.13


Cell mediated cytotoxicity

Cell-mediated Cytotoxicity

Figure 17.14


Nonspecific cells

Nonspecific Cells

  • Activated macrophages: Macrophages stimulated by ingesting Ag or by cytokines

  • Natural killer cells: Lymphocytes that destroy virus-infected cells, tumor

Figure 17.15


Self mhc restriction in the thymus

Medulla

vessel

4 - 8 +

TCR

4 + 8 -

TCR

Self MHC Restriction in the Thymus

4 low

8 low

4 -

8 low

Sub-capsular region

Productive TCR

rearrangement

Non-productive TCR

rearrangement

APOPTOSIS

4 + 8 +

TCR

Not recognise self MHC

Recognise self MHC

macrophage

4 + 8 +

TCR

TCR recognisesself antigens

Cortex

TCR does not recognise self antigens

Negative selection

Cortico-medullary region

4 - 8 -

4 + 8 +

TCR


Self mhc restriction in the thymus1

Self MHC Restriction in the Thymus


T cell clonal selection animation

T-Cell clonal selection Animation


Superantigens

Superantigens

  • Proteins produced by pathogens

  • Not processed by antigen presenting cells

  • Intact protein binds to variable region of β chain on TCR of T cells and to MHC class II on antigen presenting cells (APC)

  • Large numbers of activated T cells release cytokines having pathological effects


Conventional antigen

Conventional Antigen

Antigen presenting cell

α2

β2

α2

β2

CHO

CHO

MHC Class II

α1

β1

α1

β1

CHO

CHO

CHO

CHO

Super

antigen

Antigen

αV

αV

βV

βV

CHO

CHO

CHO

CHO

T cell receptor

αC

βC

αC

βC

CHO

CHO

CHO

CHO

T lymphocyte

Superantigen


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