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Transcript
Chapter 17- Specific Defenses of the Host :The Immune Response
Immunity:
Serology- study of reactions between antibodies and antigens
Globulins- class of proteins that include antibodies
Naturally Acquired Active immunity- antigens enter body naturally, body produces antibodies and specialized lymphocytes (ex when person get diseases can be
lifelong or confer)
Naturally Acquired Passive Immunity- passes from mother to fetus via placenta or from mother’s milk
Artificially Acquired active immunity- vaccination
Artificially Acquired Passive immunity- intro of antibodies from animal or person who is already immune, antibodies found in serum- antiserum, blood fraction rich
in antibodies called gamma globulin,antibodies-immunoglobulins
The Duality of the Immune System:
-Humoral immunity- antibody-mediated immunity- production of antibodies that act against foreign organisms and substances, found in extracellular fluids: blood
plasma, lymph, mucus secretions, B cells- responsible for antibody production, defends primarily bacteria, bacterial toxin, viruses in body fluids, transplanted tissue
-Cell-mediated immunity- T cells, act against foreign org/tis, regulate activation and proliferation of other immune system cells, most effective- bacteria and viruses in
phagocytic/ infected host cells, primary responder to transplanted tissue-foreign skin graft, mounts response to reject foreign tissue, defense against cancer
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Antigen and Antibodies:
The Nature of Antigen: provoke highly specific immunity response in organism, either proteins or large polysaccharides, lipids and n.a. antigenic when combined with
proteins and polysaccharides, components of invading microbes such as capsules, cells walls, toxins, coats, surfaces, flagella, fimbriae
Antibodies recognize and interact with specific regions on antigens- antigenic determinants (epitopes), nature depends on size, shape, and chemical nature/structure
Haptens- low molecular weight, not antigenic unless attached to carrier, hapten will react with antibody independent of carrier molecule ex: penicillin- not antigenic
but initiates immune response when combined w/ serum protein.
Nature of Antibodies- proteins made in response to antigen, can recognize and bind to antigen, help neutralize or destroy antigen, highly specific in recognizing
antigen that stimulated orig. formation
Antigen like bacterium or virus- have several antigenic determinant sites that cause pro of dif antibodies, each antibody=2 identical sites that bind to epitopes- sites
called antigen binding sites
Valence- number of antigen-binding sites on an antibody.
Structure: monomer- four protein chains: two identical light (L) chains, two heavy (H) chains, chains joined by disulfide links, other bonds to form Y-shaped molecules
( flexible, can be T shape), two sections at end of Y arms are variable (V) regions, amino acid sequences of v are identical on one antibody, structure reflects nature
of antigen for which they are specific (antigen binding sides), stem of antibody and lower parts of Y arms-constant regions: 5 major types- give major classes
of immunoglobulin, stem of Y shape- Fc region- often important in immunological reactions, if left exposed after attachment to antigen, Fc regions of adjacent
antibodies can bind to the complement, leads to destruction of bacterium.
Immunoglobulin Classes: each class = different role
B cells and Humoral Immunity: humoral carried by antibodies (prod by lymphocytes)activate B cells , process that leads to production of antibody starts when B cells
exposed to free/ extracellular antigen- B cell activated, divides, differentiates into clone of many effector cells- plasma cells, plasma cells then produce antibodies
directed against antigen that activated B cell,
-B cell from stem cells in red bone marrow in adults, liver in fetuses, after maturation, mature b cells mirgrate to lymphoid organs ( lymph nodes, spleen), once in
organs, B cells recognize by antigen receptors
-Apoptosis- rids body of unneeded cells, ex: elimination of activated macrophages terminate immune response.
Activation of Antibody Producing by Clonal Selection : antibodies in B cell surface will bind only to one specific antigen, when approp antigen bings to antigen
receptors on B cell, B cell proliferates into clones- clonal selection, antigen selects lymphocytes that will multiply to form clone with same immunological specificity.
Antigen-Antibody Binding and its Results: antigen-antibody complex- antibody binds to antigen at antigen-binding site
-binding protects host by tagging foreign cells and molecules for destruction by phagocytes and complement, antibody not damaging antigen
-Agglutination- antibodies cause antigens to clump- easily ingested by phagocytes, IgM- effective at cross linking and aggregating antigens- numerous binding sites.
-neutralization- IgG antibodies inactivate viruses by blocking their attachment to host cells, and they neutralize bacterial toxins by blocking active sites, opsonizationantigen coated w/ antibodies that enhance ingestion and lysis by phagocytic cells, antibody- dependent cell mediated cytotoxicity resembles opsonization in that the
target organism coated w/ antibodies,
-IgG and IgM antibodies trigger complement system, complements action of antibodies, inflammation-coating, - leads to attachment and activation of complement
on microbe surface, then lysis- attracts phagocytes and other defensive immune cells to area.
Immunological Memory:
-intensity of humoral response-reflected by antibody titer (amount of antibody in serum
-initial contact w/ antigen- person’s serum has no detectable antibodies for several days, slow rise in antibody titer, first IgM antibodies are produced, followed by
IgG, then gradual decline in antibody titer- pattern= primary response
- immune response of host intensifies after second exposure- secondary response=memory or anamnestic response.
T cells and Cell-Mediated Immunity: cytokines-function as chemical messengers w/i immune system, some inhibit response, others stimulate, serve as
communicators between leukocytic (white cell) populations-IL, chemokines- induces migration of leukocytes-IL8.
-interferon- help protect against viral infection of cells= cytokine.CSF( colony stimulating factors stimulate formation of various blood cells, TNF- cytokines)
Cellular Components of Immunity: T cells= key, develop from stem cells and migrate to thymus to reach maturity, next migrate to various lymphoid organs where
they are apt to encounter antigens.
-M cells (microfold)- allow pathogens to pass through, scattered number of gateway cells, located over Peyer’s patches,
-T cells use antigen receptors to recognize and react to antigen, some become memory cells.
Types of T cells: 4 functional types, classified by cell-surface receptor (CD) clusters of differentiation- CD4 (primarily Ct and long-lived memory cells and CD8 (cytotoxic
and suppressor)
1. Helper T cells- once activated by antigen, use cytokines to influence activity of other immune cells,differentiate into TH1 and TH2- produce unique
cytokines, TH1- cyto- activate cells related to cell-mediated immunity (ex:macrophages, CD8 T cells, NK cells), TH2- produce cytokines that activate
eosinophils which are protective against certain parasites, support allergic reactions and stimulate B cells to produce IgM IgE.
Helper T cell activation:
1. Antigen-presenting cell encounters and process antigen, binding of Th cell to antigen MHC complex on APC stimulates APC to secrete IL1
2. IL1 activates Th cell which makes IL2, secreted, returns to receptors on surface of same cell which then begins to proliferate and differentiate into
mature Th cells, stimulate Th cells have receptor for IL2
3. Activated Th cells begin produce IL-2 and other cytokines which then stimulatesother Th cells specific to that antigen to proliferate & mature
Cytotoxic T cells- destroy target cells on contact, viruses and some bacteria reproduce w/I host cell, cannot be attacked by antibodies, attacks virus infected host cell.
1. Tc cells binds w/ MHC antigen complex on cell surface then releases protein, perforin, forms pore in membrane of target, causing lysis
2. Tc continues until undergo apoptosis.
Delayed Hypersensitivity T cells (Td)- mostly Th cells and a few Tc cells, associated w/certain allergic reactions.
Supressor T cells- generally though to regulate immune by turning off antigen not there,temporary suppressive activity by Th and Tc cells.
Nonspecific Cellular Components:
-macrophages- phagocytic, stimulated to become activated macrophages (effective, appearance recog different, large and ruffled), stimulation by ingestion of
antigenic material. Cytokines from antigenically activated Th may activate macrophages, ability to eliminate certain virus-infected cells and pathogenic intracellular
bacteria, ability to attack & destroy cancerous cells, antigen-presenting cells.
Natural Killing Cells- certain lymphocytes, capable of destroy other cells( virus infected, tumor cells), not specific in compare w/Tc,do not need to be stimulated by an
antigen, not phagocytic but must contact target to lyse it
The Production of Antibodies: requires assistance of Th (T-dependent antigen- mainly proteins, foreign RBC, combo of haptens and carrier molecules)
1. Antigen ingested,processed by APC, fragments are presented on surface of APC, Th cell specific for antigen reacts w. MHC-antigen complex
2. Th cell reacting w/ MHC-antigen complex then produces IL-2 that influences B cell to differentiate into plasma cell that begin to produce humoral
antibodies.
-antigen that can stimulate C cells directly w/o help of T cells-T-indep antigens-usually composed of polysaccharides or lipopoly
Antibody-dep cell-mediated Cytotoxicity: w/ help of antibodies prod by humoral, cell mediated immune can stimulate NK cells and cells of nonspecific, organism such
as protozoa or helminth too large to be phagocytized can be attacked by immune system cells- antibody-dependent cell-mediated cytotoxicity (ADCC):
1. Target cell coated w. antibodies leaving Fc stem region pointing outward. 2. In addition of NK cells, variety of cells including neutro,eosino, macro-have
receptors that will bing to protruding Fc regions and target cell
2. Target cell lysed by substance secreted by attacking cells.