Ph 162A Lec 8: Adaptive, Specific Immunity

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non-specific (innate) vs. acquired (specific)

Back 1

-more rapid vs. slower
-phys, chem, bio triggers vs. chem, bio triggers
-not specific for trigger vs. specific
-has no memory vs. has memory

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acquired immunity

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specific, adaptive immunity
-active: natural via infection, artificial via immunization
-passive: natural via maternal Ab, artificial via Ab from other source

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immunogens, antigens

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-substances that induce specific immune response, specific for distinct macromolecules
-immunogens-antigen bound by Ab, recog by body as non-self and stim response
-capacity to respond is not inherent

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epitope, antigenic determinants

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smallest unit of an antigen to which the immune system respons; ie. to which an Ab or cell can bind. one antigen may have multiple epitopes.

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biochemical nature of antigens (immunogens)

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protein>carbs>DNA>lipids
lipids and DNA generally have to complex to proteins in order to be immunogenic

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weight and form of immunogen

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-heavier the molecule, the more immunogenic the antigen
-particulate molecule is more antigenic than a soluble molecule
-conformational determinants can hinder: too folded, complex struc, binding sites hidden

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foreignness

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a molecule must be foreign to the host in order to induce an immune response

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immunologic tolerance

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during dev. of fetal immune system, accepts everything as being "self" and not foreign. if a foreign molecule eg. a MO is intro'd the fetus will accept it as self and will not able to respond immmunologically to those epitopes

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route of administration and dosage

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-magnitude of response: intravenous>intramuscular>oral
-larger the dose, the greater the response

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adjuvant

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substance administered with an antigen to enhance immunogenicity of the antigen; may help by preserving antigens, promoting slow release of the antigen, and/or helping to target certain cells. eg. aluminum hydroxide

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requirement for response

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immunogens must be properly presented to cells of the immune system before those cells can respond

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MHC

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major histocompatibility complex molecules, group of cell surface molecules that determine our tissue type, also called HLA (human leukocyte antigens), must be closely matched for an organ transplant; play a role in immune response as class I or class II

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antigen presenting cells (APCs)

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phagocytize and process extracellular substances
1.)macrophages- roles in innate and adaptive response
2.)dendritic cells- involved in initiating adaptiv response
3.) B cells- lymphocytes derived from bone marrow

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MHC class II molecules

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-outside parasitized host APC (only) cell wall or membrane
-presented with phagocytosed substances
-then antigen presented to T cells --> further immune response
-prevents T cells from being activated by free floating antigens, helps control response

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MHC class I molecules

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-present on surf. of all nucleated cells
-presented with intracellular substances produced/replicated by the cell, eg. viruses

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two types of immunity

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1.) cell mediated immunity (CMI)
2.) humoral immunity (HI)

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CMI

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-involves T-cells, found in all lymphoid tissues and 75% of lymphocytes in blood
-used where antigens re embedded in cell membrane or inside host cells (eg. viruses)
-responds to antigens assoc with host's own cells, eg. intracellular bact, small things that get inside cell

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HI

Back 18

-Ab mediated- B cells; found in all lymphoid tissues and 10% of lymphocytes in blood
-effective in defending boy of bact toxins, bact, viruses, before they enter call (extracellular)
-responds to extracellular antigens eg. things too big for macrophages like helminths

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ontogeny

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development of lymphocytes
-stem cells in fetus liver and bone marrow
-bone marrow: differentiate to Bcells
-thymus: differentiate to T cells
-both go to 2* lymphoid tissues (mainly lymph nodes) to mature when stimulated by antigen

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B and T cells

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-B:memory and plasma cells
-T: memory and effector cells
-effector cells- CD4 and CD8
-CD4- helper cells, CD8-cytotoxic cells, produce cytokines

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specificity and diversity of lymphocytes

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when in bone marrow or thymus, diversity is generated, creating all the specific lymphocytes for the millions of antigens likely to be encountered. each cell is programmed to a single epitope only in small numbers unless antigenic stim occurs i.e. when the B or T cells contact its specific antigen, then there is cloncal proliferation

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primary immune response

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during initial contact of antigen with the pre-programmed lymphoctyes, creating a pool of memory cells

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secondary immune response

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-subsequent exposures, proliferation of cells with this antigenic specificity occurs more rapidly due to the memory cells--> faster and stronger

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CMI: recognition of the immunogen

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CD8 T cells (cytotoxic T cells) (Tc) recognize peptides bound to MHC I molecules eg. infected with intracellular bact or virus

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CMI: response of CD8 cells

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CD8 molecule on the surface of pre-Tc binds to MHC I molecules complexed with antigen --> activated and cell div to T cell --> perforin is release from granules within the Tc, which make pores in membrane and allow entry of Tc proteases --> antigenic apoptosis

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CMI: CD4 (helper T cell) response

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-CD4 cells have a specific MHC protein called CD4 complex
-APCs with MHC II molecule present pieces of proteins to T cell receptor (TCR)
-CD4 cells differentiate into memory T cells, and TH1 or TH2 depending on environment

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CMI: TH1 (inflammatory T cells)

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produce interferon gamma and tumor necrosis factor alpha (cytokines) that act on macrophages to increase their activation eg. killing/digestion of phagocytized intracellular materials --> amplify inflamm response and antigen presentation

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HI: TH2 cells

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cells produce interleukin (IL) 4,5, and 6 (Cytokines) which stimulate B cell differentiation and maturation to increase Ab production
-when things are too big for macrophages eg. helminth

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HI: recognition of antigen

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when reacts with TH2, receptor for antigen on B cells is immunoglobulin (Ig) which in combination with other cell membrane molecules, signals the cell to produce Ab to specific antigen it is programmed for

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HI: response

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production of antibodies (Ig's)
antibodies- proteins produced by B cells that bind with antigens with specificity and affinity

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antibodies

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-have antigen binding site which is variable region of light and heavy chains for specificity
-various classes of Ig's: IgM is 1* response but not as specific, pentamer (more antigen binding sites), IgG is 2*, monomer-more specific

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neutralization

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antibodies combine with soluble antigen and inactivate it (eg. toxins)
-on a virus it prevents it form infecting or binding host

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opsonization

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Ab combines with antigens on surface of MO and initiate a complement cascade --> neutrophils and macrophages activated --> enhances phagocytosis
-esp important in counteracting effects of capsules and surface proteins of MO's that inhibit phagocytosis