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Major Events in the Local Inflammatory Response.

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Presentation on theme: "Major Events in the Local Inflammatory Response."— Presentation transcript:

1 Major Events in the Local Inflammatory Response.
Chemical signals released by activated macrophages and mast cells at the injury site cause nearby capillaries to widen and become more permeable. Fluid, antimicrobial proteins, and clotting elements move from the blood to the site. Clotting begins. Chemokines released by various kinds of cells attract more phagocytic cells from the blood to the injury site. Neutrophils and macrophages phagocytose pathogens and cell debris at the site, and the tissue heals.

2 Acquired Immunity While pathogens are under attack by innate defenses, the intruders inevitably come into contact w/ lymphocytes (key cells of acquired immunity). EX. Macrophages (Innate) attacking microbes secrete cytokines- proteins that help activate lymphocytes and other cells of immune system. Antigen- any foreign molecule that is specifically recognized by lymphocytes Large molecules Protein or polysaccharides EX: toxins (antigen) secreted by bacteria are dissolved in extracellular fluid; other antigens protrude from surface of pathogen Lymphocyte recognizes and binds to epitope– accessible portion of an antigen.

3 Antigen receptors on lymphocytes (B/T)

4 The Interaction of T cells with MHC molecules
Class I and class II MHC molecules display peptide fragments of antigens to (a) cytotoxic T cells and (b) helper T cells, respectively. In each case, the T cell receptor binds with an MHC molecule-peptide antigen complex. Class I MHC molecules are made by most nucleated cells, whereas class II MCH molecules are made primarily by antigen presenting cells. A fragment of foreign protein (antigen) inside the cell associates with an MHC molecule and is transported to the cell surface. The combination of MHC molecule and antigen is recognized by a T cell, alerting it to the infection.

5 How do lymphocytes develop and populate in your body?
Lymphocytes arise from stem cells in the bone marrow and differentiate without any contact with antigens. B-Cells develop entirely in the bone marrow T-Cells complete their development in the thymus Mature lymphocytes, each specific for a particular epitope, circulate in the blood and lymph to various lymphoid tissues, where they encounter antigens.

6 Immunoglobulin gene rearrangement

7 Clonal Selection of B Cells
Antigen molecules bind to the antigen receptors of only one of the three B cells shown. The selected B cell proliferates, forming a clone of identical cells bearing receptors for the selecting antigen. Some proliferating cells develop into short-lived plasma cells that secrete antibodies specific for the antigen (Effector Cells). Some proliferating cells develop into long-lived memory cells that can respond rapidly upon subsequent exposure to the same antigen (Memory Cells).

8 The specificity of immunological memory.
Day #1: First exposure to antigen A Primary response to antigen A produces antibodies to A Day #28: Second exposure to antigen A; first exposure to antigen B. Secondary response to antigen A produces antibodies to A; primary response to B produces antibodies to B.

9 Confused by all the different cell names?
B cells make antibodies, which provide humoral immunity. This helps fight pathogens that are circulating in body fluids. Cytotoxic T cells destroy body cells that are infected by a pathogen or cancer cells. Helper T cells activate both B and T cells Humoral Immune Response involves activation and clonal selection of B cells, resulting in the production of secreted antibodies. Cell Mediated Immune Response involves activation and clonal selection of cytotoxic T cells, which directly destroy certain target cells.

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11 Role of Helper T Cells in Humoral/Cell Mediated Response
After dendritic cell engulfs and degrades a bacterium, it displays bacterial antigen fragments (peptide) complexes w/ class II MHC molecule on the cell surface. A specific helper T cell binds to the displayed complex via its TCR w/ the aid of CD4. This interaction promotes the secretions of cytokines by the dendritic cell. Proliferation of the T cell, stimulated by cytokines from both the dendritic cell and the T cell itself, gives rise to a clone of activated helper T cells (not shown) all w/ receptors for the same MHC-antigen complex. The cells in this clone secrete other cytokines that help activate B cells and cytotoxic T-cells

12 CTC- eliminate infected body cells and cancer cells
A specific cytotoxic T cell binds to a class I MHC-antigen complex on a target cell via its TCR w/ the aid of CD8. This interaction, along with cytokines from helper T cells, leads to the activation of a cytotoxic cell. The activated T cell releases perforin molecules, which form pores in the target cell membrane and proteolytic enzymes (granzymes), which enter the target cell by endocytosis. The granzymes initiate apoptosis w/in the target cells, leading to fragmentation of the nucleus, release of small apoptopic bodies, and eventual cell death. The released cytotoxic T cell can attack other target cells.

13 B Cells: Response to extracellular pathogens (Humoral Response)
After a macrophage engulfs and degrades a bacterium, it displays a peptide antigen complexed with a class II MHC molecule. A helper T cell that recognizes the displayed complex is activated with the aid of cytokines secreted from the macrophages forming a clone. A B cell that has taken up and degraded the same bacterium displays class II MHC-peptide antigen complexes. An activated helper T cell bearing receptors specific for the displayed antigen binds to the B cell. This interaction, with the aid of cytokines from the T cell, activates the B cell. The activated B cell proliferates and differentiates into memory B cells and antibody-secreting plasma cells. The secreted antibodies are specific for the same bacterial antigen that initiated the response.

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