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Immune System Notes I. Critical Vocabulary A. Immune System: a set of glands, tissues, cells, and dissolved proteins that combine to defend against “non-self” entities B. Antigen: any “non-self” chemical that triggers an immune system response. Antigens are often naturally occurring molecules (protein, glycoprotein, or polysaccharide) on the surface of cells and viruses C. Pathogen: any antigen that causes a disruption in homeostasis a.k.a. normal, disease free, functions D. Antibody: a protein produced specifically in response to the presence of an antigen - neutralizes antigen by bonding to the antigen E. White Blood Cells (wbc’s): a set of cells called lymphocytes, that free-float in the blood and lymph fluid - active in the immune system II. Immune System Response Overview Antigen ("non-self" entity) celluar, viral, other Specific Response (humoral) via the production of antibodies Memory Response Non-Specific Response Specific Response (cell mediated) via the destruction of infected cells Memory Response III. Non-Specific Response (first line of defense) A. The Skin 1. pH: 3-5 2. normal bacterial flora B. Mucous Membranes ex: respiratory and digestive tracts C. Specialized phagocytic white blood cells (wbc’s) that perform phagocytosis = “cell eating” ex: Macrophages: large amoeboid cells, that consume “nonself” cellular or non-cellular material D. Antimicrobial Protein ex: complement proteins: cell lysing activity E. Inflammatory Response 1. vasodialation: blood vessels become more permeable 2. complement proteins attract phagocytes 3. macrophages consume pathogens and related debris 4. high fever triggered by chemicals released by wbc’s IV. Cell Surface Molecular Markers A. Major Histocompatibility Complex (MHC) 1. recognition mechanism a. distinguish self from non-self 2. set of 20 genes w/100 alleles for each gene 3. MHC genes code for glycoproteins embedded in the plasma membrane a. cells use to detect the immediate environment 4. virtually impossible for two individuals to have the matching set of MHC markers, except identical twins 5. two classes of MHC molecules a. class I MHC: all nucleated cells b. class II MHC: lymphocytes (macrophages, B and T cells) V. Humoral Response (specific) A. Specificity ex: produces antibodies in response to non-self entities such as toxins, free bacteria and viruses B. Cells Involved (lymphocytes - active form called effector cells) 1. B-cells a. originate and mature in bone marrow b. activated B-cells become plasma cells and secrete antibodies the point of the humoral response! c. humoral response only 2. T-cells a. originate in bone marrow - mature in the Thymus gland b. of the three types, only helper (TH) T-cells participate in the humoral response C. Activation of B-cells (two types of activation) 1. Clonal selection a. B-cells directly stimulated to secrete antibodies b. large number of different B-cells 1. pre-determined during embryonic development c. antigen receptors (in the form of antibodies) on the surface of B-cells bind to free-floating antigens 1. based on antigen-receptor specificity d. once the antigen is bound to the receptor, the B-cell is stimulated to clone itself (millions of times over) * activated immune system cells are called effector cells 1. first type of clone: plasma cells: secrete antibodies 2. second type of clone: memory B-cells (details later) e. antibodies secreted into the blood and lymph bind to the original antigen *tagging the antigen for consumption by a phagocyte Clonal Selection Figure QuickTime™ and a TIFF (LZW) decompressor are needed to see this picture. 43.6 Pg. 905 special note: the captions in the textbook for this graphic are important to review Clonal Selection click here for video animation 2. T-dependent a. antigen binds to specific antigen-receptor on a macrophage 1. t-dependent antigen (cannot directly stimulate B-cells) b. involves macrophages and TH cells c. macrophage consumes the pathogen 1. in the dermis and in mucous membranes the most prevalent macrophage is a dendritic cell d. antigen fragments bind to MHC II proteins and are presented on the surface of the macrophage e. CD4 receptors on TH cell bind to antigen/MHC II complex f. Th are activated, become effector cells and form clones g. activated TH secrete cytokines which stimulate B-cells h. effector B-cells form clones: antibody secreting plasma cells i. most antigens are T-dependent Fig 43.13 - pg. 911 B-Cell Activation Due to T-Cell Dependent antigen QuickTime™ and a TIFF (LZW) decompressor are needed to see this picture. special note: the captions in the textbook for this graphic are important to review VI. Molecular Basis of Antigen-Antibody Specificity A. Antibodies do not generally recognize antigens as a whole 1. epitope: small, specific regions of the antigen’s structure that fit into the antigen-binding site of the antibody B. A given antigen may have multiple epitopes on its surface multiple antibodies may bind to the same antigen C. Antibodies are proteins called immunoglobulins (Igs) 1. Y-shaped w/4 polypeptide chains 2. do not directly destroy pathogens 3. antibodies block viral attachment site, or bacterial toxin 4. antigen-antibody complex tags pathogen for destruction by a macrophage Humoral and Antibody-Antigen Graphics QuickTime™ and a TIFF (LZW) decompressor are needed to see this picture. Fig. 43.14 Fig. 43.15 QuickTime™ and a TIFF (LZW) decompressor are needed to see this picture. click here for video Fig. 43.16 VII. Cell Mediated Response (specific) A. Specificity 1. produces cytotoxic T-cells (TC) which attack and destroy infected cells and cancer cells a. many pathogens, including ALL viruses, are obligate intracellular parasites B. Activation of TC cells 1. intracellular parasites are consumed by macrophage 2. MHC II-Antigen complex is recognized by CD4 TH cell 3. TH cell secretes a cytokine called Interleukin-2 which activates TC and Bcells QuickTime™ and a TIFF (LZW) decompressor are needed to see this picture. Fig. 43.11 C. Active TC cells (effector cell - following stimulation by Interl-2) 1. effector TC cells are called CD8 cells - named for the CD8 protein associated with the T-cell receptor protein 2. infected host cells present pathogenic antigens embedded in a MHC I protein on its surface (recall all nucleated cells have) 3. T-cell receptor binds with MHC I-Antigen complex with help from the CD8 protein 4. TC cell secretes the protein perforin which lyses the infected cell -or- the cancer cell 5. effector TC can bind to and destroy multiple cells. QuickTime™ and a TIFF (LZW) decompressor are needed to see this picture. Fig. 43.12(a) A cytotoxic T-cell (Tc) that has already lysed a cancer cell Figure 43.12 QuickTime™ and a TIFF (LZW) decompressor are needed to see this picture. VIII. Secondary Immune Response/Memory A. Result of exposure to previously encountered antigen 1. 3-5 day response time vs. 5-10 day primary response 2. immunity lasts longer 3. antibodies produced are more effective B. Performed by memory cells 1. produced during 1˚ response 2. not active during 1˚ response 3. activated by the original antigen 4. when activated - rapid proliferation to form newly cloned effector cells and, in some cases, more memory cells. Fig. 43.7 Immunological Memory QuickTime™ and a TIFF (LZW) decompressor are needed to see this picture. IX. Suppressor T cells (TS) A. Function to suppress the immune system when the antigen in question is no longer present B. TS are not well understood. C. May be effective in stopping a immune response through hormonal secretions. X. Acquired Immunity A. Active Acquired Immunity 1. dependent on person’s own immune system 2. based on non-disease causing antigens that stimulate an immune response 3. acquired via vaccines or blood transfusions (rare) B. Passive Acquired Immunity 1. transferred from one person to another a. mother to fetus b. mother to baby via mothers milk QuickTime™ and a TIFF (LZW) decompressor are needed to see this picture. Fig. 43.10 Summary of the Immune Responses