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1 Acquired Immunity

2 Defensive mechanisms include : 1) Innate immunity (Natural or Non specific) 2) Acquired immunity (Adaptive or Specific) Cell-mediated immunity Humoral immunity

3 Two mechanisms 1) Humoral immune response: - Antibodies are produced by B-lymphocytes - These have the ability to recognize and bind specifically to antigen that induced their formation 2) The cell mediated immune response (CMI) - It is mediated by certain types of T-lymphocytes - T-lymphocytes recognize foreign material by means of surface receptors TCR - T-lymphocytes attack and destroy foreign material directly or through release of soluble mediators i.e. cytokines - Attack intracellular antigen

4 1) Highly specific for the invading organism 2) Discrimination between self and non self molecules The response only occurs to non self molecules 3) Diversity: - It can respond to millions of different antigens - Lymphoctes population consists of many different clones (one cell and its progny) - Each clone express an antigen receptor and responds only to one antigenic epitope

5 Steps of Acquired Immune Response lymphocyte B & T: 1. Recognition of the antigen by specific lymphocytes 2. Activation of these specific lymphocytes 3. Proliferation and differentiation into effector cells; 4. The effectors cells eliminate the antigen 5. Return of homeostasis and development of memory cells * Memory cells evoke a more rapid and long response on reexposure to same antigen

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7 Maturation events of T lymphocyte Hematopoietic progenitors cells from bone marrow move into Thymus gland At thymus it is called thymocytes and it run through several selection process 1. Beta selection: active proliferation and elimination thymocytes with gross defects introduced into the T cell receptor (TCR). 2. positive selection: selects cells with a TCR that able to bind MHC class I or II molecules with weakest affinity. 3. Negative selection: Killing by apoptosis T cells with a high affinity for self peptides or MHC. Eliminate auto reactivity towards self.

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11 Upon maturation two types of T Lympocytes is produce which is CD4 + : T-helper cells CD8 + : T-cytotoxic cells When antigen enter a body it will be attacked by antigen presenting cells (APC). Then it will display antigen peptide bonded with MHC II on cells surface. To activate CD4+ T cells, TCR on Tcells have to bind to MHC II on APC. (first signal) Then CD28 molecule have to bind to B7 molecule (costimulation)

12 CLONAL EXPENSION Upon activation the CD4 + T Cells become blast cells. 24H IL-2 secreted and CD4 + T multiply. CD4 + T differentiate into subset(effector cells) T H 1 T H 2 Effectors cell function affects CD8 + T cells (Discuss next) B lymphocytes (Discuss next in B-lymphocytes) Myeloid cells Bone marrow precursor

13 When the antigen have been eliminated the T cells number have to be decrease. They are reduce by apoptosis. Some will remain as memory cell and can be activated without the need for CD28-B7 co-stimulation.

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16 CD8 + T lymphocyte is also called cytotoxic T lymphocytes (CTL) which mean it destroy infected host cells. CTL cell once matured is released into blood stream. Activation of CTL required binding of TCR to MHC I on APC and binding of B7-CD28. Activated CD4 + T lymphocyte can also activated CTL by releasing IL-2.

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18 When attached to infected/dysfunctional somatic cells, CTL release the cytotoxins perforin and granzymes. Perforin forms pores (aqueous channels) in the target cell's plasma membrane Allowing granzymes, to enter the target cell, which lead to apoptosis. Other mechanisms is to induce apoptosis is via cell-surface interactions between the T C and the infected cell. Elimination of excess CTL in absent of antigen is same as CD4 + T cells.

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21 Humoral is mediated by B lymphocytes principal functions of B-cells are make antibodies against antigens, perform the role of antigen-presenting cells (APCs), Develop into memory B cells after activation

22 B cells (maturation) Immature B cells are produced in the bone marrow from hematopoietic stem cells. Here stem cell develop into Pro-B cells Pro-B cells develop into Pre-B cells Then Pre-B develop into immature B cells Any cells that failed developing into immature B cells is destroyed by clonal deletion. Some immature B cell develop into IgM + IgD + mature B cells. migrate to secondary lymphoid tissues to matures.

23 B cells recognize their antigen in its native form. They recognize free (soluble) antigen in the blood or lymph using their B cell receptor (BCR) on cell surface or membrane boundimmunoglobulin

24 Activation of B lymphocytes can occur in two manner T-dependent activation T-independent activation * T = Thymus

25 T-dependent activation Once a pathogen is ingested by an antigenpresenting cell (APC) such as a macrophage or dendritic cell, the pathogen's proteins are then digested to peptides and attached to a class II MHC protein. It is detected by T lymphocyte and T H helper cells (CD4+ T cells ) is generated. T H cell then bind to specific B lymphocytes TCR on T H cells have to bind to MHC II on APC. (first signal) Then CD28 molecule have to bind to B7 molecule (costimulation)

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27 T H cell secretes cytokines that activate the B cell. These cytokines trigger B cell proliferation and differentiation into plasma cells. Isotype switching to IgG, IgA, and IgE Memory cell generation

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29 Some antigen known as TI antigens can directly activate B Lymphocytes. Two types of T-independent activation Type 1 T cell-independent (polyclonal) activation (more than 1 antigen bind to BCR on a B cells) Type 2 T cell-independent activation (in which APC present several of the same antigen in a way that causes cross-linking of antibodies on the surface of B cells).

30 Effect of T-independent activation is Plasma cell produce Proliferation of B lymphocyte Only IgM produce No memory cells produce

31 Thanks

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