7/12/12

Cell-Mediated immune response of a mature Recognition and the binding

lymphocyte to an antigen lymphocyte to divide rapidly. induces the This proliferation of lymphocytes is called clonal selection. Two types of clones are produced: short-lived activated effector cells and long-lived memory cells These effector cells activate B cells or Macrophages, or destroys infected, tumor, or transplanted cells directly or through release of soluble mediators i.e. cytokines and Controls 7/12/12

It is based on type of microbial invaders those are faced by immune system. Microbial invaders fall into two broad categoriesIn one category-organisms that originate outside the body including most bacteria, fungi as well as many protoza and invading helminths. The second category consists of the organisms that Click originate or to edit Master the bodys own cells including live inside subtitle style viruses and intracellular bacteria or protozoa. Cell mediated immune system is directed against intracellular or endogenous invaders that invade cells.

Why it is known as cell mediated

7/12/12

How the antigen is presented to lymphocytes

All nucleated cells of body trap endogenos antigens with the help of MHC 1 receptors on their surface and then present to cytotoxic T- lymphocytes also having receptors for trapping.

Its the main way of cell mediated immunity.

7/12/12

Professional antigen presenting cells also help in

Types of antigen presenting cells (APC)

1. Dendritic cells
Phagocytic dendritic cells (DC) of tissues (Most potent stimulators of T cell responses) Germinal Center Dendritic Cells (GCDCs) Thymic Interdigitating Dendritic Cells (IDCs) Interstitial Dendritic Cells

2. B cells as APC Present Ag to T cells (TH2) 3. Macrophages

7/12/12

The Role of the MHC

In infected cells, MHC molecules bind and transport antigen fragments to the cell surface, a process called antigen presentation. T cell can then detect the antigen fragment displayed on the cells surface. Depending on their source, peptide antigens are handled by different classes of MHC molecules, mainly 2 are involved in the cell mediated immunity which are as follows7/12/12

The Two Classes Of MHC Molecules

MHC Class I
Class I MHC molecules are found on almost all nucleated cells of the body and Presents Ag derived from intracellular source/cytosol. They display peptide antigens to cytotoxic T cells cytotoxic T cells kill target
7/12/12

MHC Class II
Class II MHC molecules are located mainly on dendritic cells, macrophages, and B cells and Present Ag derived from extracellular or cell-bound source.

These antigen-presenting cells then display antigens to inflammatory T cells and helper T cells.

7/12/12

T Cells
Originate in stem cells in bone marrow Change to T cells in thymus Become sensitized to specific antigen Produce cell-mediated immunity following T cell activation (in peripheral lymphoid organ) Cytotoxic T cells (Tcyt) Kill infected target cells Inflammatory (TH1) and Helper (TH2) T cells Activation of other cells (macrophages and 7/12/12 B cells, respectively)

Way of functioning of Tcells

Inflammatory T cells = TH1

Activate macrophages MHC class II-restricted Helper T cells (TH2)

Help to eradicate extracellular pathogens Activated helper T cells secrete cytokines that other lymphocytes and Provide

stimulate 7/12/12

Cytotoxic T cells = Tcyt

v

Recognize virus-infected cells Kill infected cells directly by inducing apoptosis (programmed cell death cell suicide) MHC class I-restricted

Natural Killer Cells

Recognize virus-infected cells and cancer cells They directly release lethal chemicals, leading to
7/12/12 apoptosis

Helper T cells
Participate in both the Humoral and CellMediated Immune Responses The HIV virus attacks Helper T cells

7/12/12

Slide 31 of 46

T- cell receptor
Each T cell receptor consists of two different polypeptide chains. The tips of the chain form a variable (V) region; the rest is a constant (C) region. T cells can bind tosubtitle style that is free or on the Click to edit Master an antigen surface of a pathogen A single T cell has about 100,000 identical antigen receptors.
7/12/12

Fig. 43-9

Anti

bind

g e n i n g
V

Disu

site

Li

C C brid g h t

l f i d e g e

Antige n binding si t e Vari

Anti

bind V C V site C

g e n i n g

c (a) B cell e l recept l or

a i n Heavy ch ain Cytoplasm of s B cell

ch

V C

a b Constl a e regi n t o Transmemb regio n rane n region s s Plasm a memb r a n e

c Disulfide h bridg a Cytoplasm of e iT cell n (b) T cell recept or

c h a i n

c e l l

7/12/12

Steps of the Cell Mediated Response

1.

Infected cell presents antigen on Class I MHC

2.

Cytotoxic T Cell recognizes antigen and binds to it

7/12/12

Slide 27 of 46

Steps of the Cell Mediated Response

3. Cytotoxic T Cell reproduces (clones
itself) 4. Cytotoxic T Cells bind to antigen bound to infected cells and release perforin to lyse infected cells

7/12/12

Slide 28 of 46

7/12/12

Slide 26 of 46

Cytotoxic T cells are the effector cells in cell-mediated immune response. Cytotoxic T cells make CD8, a surface protein that greatly enhances interaction between a target cell and a cytotoxic T cell. Binding to a class I MHC complex on an infected cell activates a cytotoxic T cell and makes it an active killer. The activated cytotoxic T cell secretes proteins that destroy 7/12/12 the infected target cell.

Cytotoxic T Cells: A Response to Infected Cells

Fig. 43-17

Antige npresen tin Bacteriu g cell m

Peptide antige n Class II MHC C molecule D cell TCR (T 4 receptor) Helper T cell + + Cytotoxic T cell

Humoral immunity (secretio n of antibodie s by plasma cells )

Cytokin es + B c e l l

Cellmedi ated immunity (attack on infected cells )

7/12/12

Memory T-cells

7/12/12

Overall diagramatic presentation of 7/12/12 cell mediated immunity

Primary versus Secondary Response

Primary Response = initial immune response to antigen

The first exposure to a specific antigen represents the primary immune response

During this time, effector B cells called plasma cells are generated, and T cells are activated to their effector forms

7/12/12

Secondary Response = immune response when

Primary vs. Secondary Response

More antibody & T cell production in a shorter amount of time

The secondary response is much faster than the primary response

Secondary Response

Primary response

7/12/12

Slide 30 of 46

Thanks
Click to edit Master subtitle style 7/12/12