05. AMI, CMI, immunization.doc

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D’YOUVILLE COLLEGE
BIOLOGY 307/607 - PATHOPHYSIOLOGY
Lecture 5 - IMMUNE RESPONSES, IMMUNIZATION
Chapter 5
1.
Antibody-Mediated Immunity (AMI):
• antibodies – Y-shaped protein molecules produced by B cells
- secreted by stimulated mature B cells (plasma cells) & freely circulate in
plasma as immunoglobulins
- FC fragment (= stalk of Y) binds to surfaces of defensive cells that express
FC receptors (e.g. phagocytes, mast cells, NK cells)
- different classes of antibody (immunoglobulin) have different FC
fragments
- FAB fragments (= branches of Y) bind to unique epitope of antigens
- antigen-antibody binding results in:
- neutralization of toxins
- agglutination (clumping) of cell-bound antigens
- precipitation of soluble antigens
- complement fixation
- above results promote phagocytosis (opsonization), inflammation
(stimulation of mast cells, chemotaxis) and lysis of offending cells (activated
complement and activated NK cells) (figs. 5 – 3, 5 – 6 & ppts. 1 & 2)
• immunoglobulins (fig. 5 – 5 & ppt. 3) – freely circulating antibodies
constitute a fraction of plasma proteins
- five categories (ppts. 4 & 5) – IgM (pentamer - fig. 5 – 4), IgG
(commonest), IgA (often a dimer – found in external secretions), IgE (low
concentration, involved in parasitic infections and in allergies), & IgD (lymphocyte
antigen receptor)
- IgM produced first in initial response (mainly to bacterial infections),
followed by IgG; both are complement-fixing antibodies; IgM is dominant in
agglutination reactions; secondary response produces mainly IgG
- IgE binds (via Fc component) to eosinophils to promote anti-allergen &
anti-parasitic reactions
Bio 307/607 lec 5
- p. 2 -
Bio 307/607 lec 5
- p. 3 -
• sensitization:
- B cells activated by antigen binding proliferate a population of plasma
cells (secrete antibodies specific for stimulating antigen) as well as ‘memory’ cells
(ppt. 6)
- antibody titer (specific for activating antigen) rises (fig. 5 – 10 & ppt. 7)
- B cell activation is facilitated by lymphokines (interleukins) from
activated T helper cells (TH2)
- clonal expansion (plasma & memory cell formation) can be
undertaken by B cells with or without the intervention of helper T cells
- once established, the specific B cell clone can respond more rapidly
and vigorously on subsequent encounters (immunological learning & memory)
- antigen-presenting cells (APC) are cells that have phagocytized or bound
antigen (macrophages, B cells, dendritic cells)
- antigens are presented on surface in association with MHC markers
(class II) (ppt. 8)
- T cells (specific clone that can bind to the MHC as well as to the
displayed antigen) are activated by antigen recognition (clonal selection)
- APCs secrete interleukin 1 that stimulates proliferation of a clone of
active helper cells as well as ‘memory’ cells (known as clonal expansion; see figs. 5 –
8, 5 – 9 & ppts. 9 & 10)
2.
Cell- Mediated Immunity:
• TH1 cells interact with APCs and undergo clonal expansion (fig. 5 – 8 &
ppts. 9 & 10)
- these helper cells facilitate clonal expansion or other cells specific for
same antigen via secretion of lymphokines
- cell types stimulated by lymphokines include cytotoxic T cells, NK cells &
macrophages (fig. 5 – 11 & ppts. 11 - 13)
Bio 307/607 lec 5
- p. 4 -
- activated TC-cells recognize & kill virus-infected or parasite-infected
cells, which display antigen in association with MHC class I molecules (bind with Tcell receptor aided by CD8) (ppt. 14)
- activated NK cells recognize & kill virus-infected cells & tumor cells
(tumor surveillance) (ppt. 15)
- healthy cells display MHC I alone & inhibit NK cell activity, whereas
antigen in association with MHC class I elicits cytotoxic response from NK cells
• summary (ppts. 16 & 17)
3.
Active and Passive Immunization:
• vaccination: active immunization with sensitizing dose of antigen
- vaccines (table 5 - 3) are prepared from dead microorganisms, weakened
microorganisms (attenuated), or inactivated exotoxins of microorganisms
- administration of vaccine elicits primary immune response so that
subsequent natural exposure to the antigen will be vigorously and rapidly
dispatched; an otherwise dangerous or lethal first encounter can be avoided
• antiserum administration: passive immunization with antibodies from
donor with immunity or manufactured antibodies (monoclonal antibodies)
- provides temporary protection from infective organisms or their toxins,
e.g. inoculations for travelers to exotic locations
- provides protection during immune system’s development of sensitization
to an infection, e.g. rabies shots
- may be used to prevent sensitization to Rh incompatibility between
mother and fetus, e.g., administration of anti-Rh following any birth involving Rh
incompatibility (fig. 5 – 13 & ppt. 18)
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