Immune System

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innate (non-specific)

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- generalized immune response, are not antigen-specific
- 1st line of generalized defense
- phagocytic cells, granular leukocytes, attack all infectous agents
- natural killer cells (NK): separate class of lymphocyte that attack virus-infected cells or tumor cells
- humoral factors

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humoral factors for innate

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- cytokines = different class of small proteins that are secreted by a variety of cells, are not antigen-specific, but fcn to coordinate and enhance immune responses
- complement system = series of plasma proteins, which when activated can lyse microorganisms and stim phagocytic cells

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specific/adaptive (aquired) immunity

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- specificity: individual B and T cells recognize specific domains of antigens
- diversity: lymphocytes utilize molecular mechanisms to modify their receptors so they can respond to a large number of different antigen domains
- memory: after first exposure to a antigen, memory cells and clonal expansion allow for rapid response
- self limitatoin: once the antigen is neutralized, the response ceases
- tolerance: lymphocytes undergo selection mechanisms that eliminate lymphocytes expressing receptors for self proteins
- humoral factors

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humoral factors for aquired

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- immunoglobins (antibodies, Ab); secreted by B cells
- lymphokines = type of cytokine secreted by T cells

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major histocompatability complex (MHC) molecules

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- specific cell surface protein sequences that are found on all nucleated cells and platelets. Each individual has a different "fingerprint" arragment of MHC molecules

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MHC I molecules

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- found on all nucleated cells and displays all protein sequences actively syn by the cell, representative map of proteins that are expressed on that cell

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MHC II molecules

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- found only on antigen-presenting cells (APCs) and display partially digested foreign proteins to Helper T cells, foreign antigens can be taken up by the cell and they are mixed with the MHC II cells and then that is what is present on the surface of the cell

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development

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during development, B and T cells aquire the ability to distinguish b/w self and non-self antigens and develop surface receptors for specif antigens, development of lymphocytes is a multi-step process with many stages in cell maturation

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antigen-presenting cells

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- these cells have surface MHC class I and II. Some, but not all APCs are phagocytic. APC have the ability to endocytose and digest infectous agent proteins making them into smaller peptides which are then complexed [mixed] with MHC II molecules and deposited on the surface of APC. T Cells receptors can then bind smaller MHC-complexed antigens. T cells cant bind to the foreign antigen unless it has first become mixed with the MHC II

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T lymphocytes

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- have receptors (TCR) that bind to antigen-MHC complexes. Since T lymphocytes actually bind foreign antigens, it is referred to as cellular immunity
- express cell surface clusters of differentiation molecules (CD molecules) that act as co-receptors and mediate T cell activation. Expression of CD molecules develops in the thymus.
- binding of antigen-MHC complexes to TCRs along with CD molecules interactions stim T cell activation. T cell activation involves cellular proliferation and secretion of cytokines (lymphokines). Requires two signals: receptor binding to foreign antigen and the CD
-- lymphokines perform a variety of immune functions including activation of other T cells, NK cells and stim of B cell differentiation into plasma cells

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CD4+ T helper cells

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- recognize and bind to antigen-MHC II complexes on APC
- different subtypes based on lymphokines that they secrete
- faciliate differentation of B cells into plasma cells
- interact with other T cells

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CD8+ cytotoxic T cells

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- recognize abnormal MHC I on transformed cells
- destroy transformed cells by 2 mechanisms:
--release perforins which induce cell memb damage
-- activate genes which regulate apoptosis in transformed cells

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suppresor T cells

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decrease activity of B and T cells

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memory T cells

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after the first exposure, you have T cell activation and proliferation

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B lymphocytes

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- respond to cell-bound or cell-free antigens
- helper T cells mediate B cell activation which involves cellular proliferation and B cell differentiation into plasma cells
- B cells syn immunoglobins which are membrane bound in immature B cells and secreted by plasma cells. circulating immunoglobins are referred to as Abs. Since circulating Abs bind to foreign antigens, it is referred to as humoral immunity

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antibodies

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- bind to foreign antigens and facilitate phagocytic cells into destroying it
- they are glycoproteins which act as flexable adaptors which can bind to antigens as well as bind to other phagocytic cells [Fab fragment bind to antigen, Fc fragment bind to phagocyte]
- immature B cells express memb-bound immunoglobin (IgM) on their surface. Complexed with Iga and Igb, it acts as a B cell antigen receptor (BCR) and serves as the antigen binding site
- during B cell activation, antigen binds to BCR and it is endocytosed, partially digested and complexed with MHC II molecules. B cells act as APC allowing helper T cells to bind to the antigen
- helper T cells secrete lymphokines which stim B cell differentiation into plasma cells as well as proliferation of memory B cells
- B cell differentiation involves first the conversion of IgM to IgD, after final differentiation into plsma cells, Igs are syn in a soluble form and then secreted

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IgM

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first Ab produced by B cells, activates complement system

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IgG

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most abundant Ab, activates complement system, only Ab that can cross placenta

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IgE

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attaches to mast cells and basophils and mediates the release of histamine, heperin, etc. from these cells during an allergic response

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IgA

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produced by plasma cells in the mucosa of organs, found in body secretions

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IgD

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bound to surface of B cell plasma memb, acts as a B cell receptor

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primary and secondary immune response

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each B and T cell carries receptors for specific antigen domains, therefore, under normal conditions there will be a small amount of each type of lymphocyte present in the pody

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1st exposure to a specific antigen

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primary immune response TO primary response: lymphocytes proliferate and differentiate:
1. effector cells: cytotoxic T cells, plasma cells
2. memory B and T cells: more rapid and expanded response
TO clonal expansion: expand proliferation to produce many antigen specific cells

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2nd exposure to a specific antigen

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CLONAL EXPANSION