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The Immune System protects by _________.
Self vs. non-self discrimination
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Antigen = compounds known to cause __________.
antibody response to be generated
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Two broad means by which the Immune system deals
- with pathogens
- Acquired (Specific or Adaptive) Immunity
- Innate (Nonspecific or Natural) Immunity
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Innate immunity
- immediate: 0-4 hours
- Infection ->
- Recogntion by preformed, nonspecific and broadly specific effectors ->
- Removal of infectious agent
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Early induced innate response
- early: 4-96 hours
- Infection ->
- Recruitment of effector cells ->
- Recognition of PAMPS. Activation of effector cells and inflammation ->
- Removal of infectious agent
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Adaptive immune response
- late: >96 hours
- Infection ->
- Transport of antigen to lymphoid organs ->
- Recognition by naive B and T cells ->
- Clonal expansion and differentiation to effector cells ->
- Removal of infectious agent
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Comparison of Innate and Adaptive Immunity
- Innate Immunity: No time lag; Not antigen specific; No memory
- Adaptive Immunity: A lag period; Antigen specific; Development of memory
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Schematic structure of antigen receptors
- Variable region - antigen binding; fine tuning
- Constant region - effector
- Similar between Ab and T-cell surface receptor
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Structure of Ig
- Two heavy chains - disulfide bonds
- Two light chains - linked to heavy chains via disulfide bonds
- Both chains are made of variable and constant regions.
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________ are the molecules recognized by the immune response; ______ are regions to which ______ bind.
- Antigens
- Epitopes
- antigen receptors (of Abs), aka paratope
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Papain cleaves Ig into __________; pepsin cleaves Ig into __________.
- 2 Fab (fragment antigen binding) and Fc (fragment crystalizable)
- F(ab')2 interconnected and 2 pFc' (multiple pieces due to multi-site cleavage)
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The course of a typical antibody response
- lag phase + primary response (novel antigen)
- Secondary response
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In a primary response the first class of Ab detected is usually ___. _______ is said to occur when the constant heavy chain of the Ab changes to other isotypes.
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The immunoglobulin isotypes are encoded by ______.
a cluster of Ig heavy-chain C-region genes
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In secreted form, IgA is in the form of a ___ that is hooked by the ____; IgM ____ (hexamer of IgM also exists but is rare).
- dimer
- J chain
- pentamer by J chain
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Valency and avidity of Ab-Ag interactions
- how many valent bonds used per Ig to bond Ag - monovalent, bivalen, polyvalent.
- the level of interaction: more bond, higher avidity. low, high, very high
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Highest molecular size of Ig of different classes
IgM, most labial, degrades easily
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Serum level of Ig
- IgG is the highest, followed by IgA
- IgE is the lowest
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Half life of Ig
IgD and IgE are the shortest.
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Ig light chain isotypic variants
- kappa (Κ)
- lambda (Λ)
- Encoded by different genes at different loci
- Either type can combine with any heavy chain
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T cell receptors
- alpha and beta chains
- both have variable and constant regions
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Cytokines:
- Released by leukocytes & other cells
- Chemical messengers
- Balance between cell mediated & adaptive immunity
- Pleiotrophy (more than one action; contrary to redundancy)
- Autocrine (act on producing cells)
- Paracrine (act on cells other than producers)
- Antagonism (one cytokine may act against another)
- Lymphokines are produced by lymphocytes (no longer valid definition); Monokines are produced by monocytes and macrophages (no longer valid definition); Old names have stuck!
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Chemokines:
- Chemoattractant cytokines produced in earliest
- phase of infection and other immune responses; attract other cells.
- CXC (two invariant cysteines separated by a single AA) chemokines
- CC (two invariant cysteines) chemokines
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Cluster of differentiation Ags
- CD
- Cluster of antigens with which Ab react, and that characterize cell surface molecules
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Two major types of Cells involved in Host Defense:
B and T cells
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B cells mature into _______ – making
- _________ (“______” arm of host defense)
- antibody producing plasma cells
- immunoglobulins
- humoral
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heavy chain
- - Ig classes - IgM, IgD, IgG, IgA, & IgE. Determined by H chain
- Ig isotypes are determined by sequences in the H (µ, δ, γ, α and ε, respectively), and light (L) chains (λ and κ)
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T cells constitute the ____ arm of host defense.
cellular
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Components of the immune system:
- 1. Many are actually cellular in nature and not associated with any specific organ but rather are embedded or circulating in various tissues located throughout the body.
- 2. Many are proteins that circulate to direct or attract cells of the immune system to their target sites.
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Distribution of lymphoid tissues in the body
- Central (primary) lymphoid organs
- Peripheral (Secondary) lymphoid organs
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Central (primary) lymphoid organs
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Peripheral (Secondary) lymphoid organs
- Sites of activation
- lymph nodes
- Spleen
- Mucosa associated:
- - gut-associated tonsils
- - Peyer’s patches - small nodes lining the small intestines
- - appendix
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The spleen
- Red pulp: Site of RBC destruction
- White pulp: Lymphoid cells; from circulation.
- - contains central arteriole surrounded by lymphoid sheath with lymphoid cells, B-cell area, etc.
- Structure is similar to lymph nodes.
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The spleen has no connection with the lymphatic
- system; all cells enter the spleen from _____ and
- exit directly back into it.
- the blood
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Lymph node
- Paracortical area - T cells
- Primary lymphoid follicle - naive/virgin B cells
- Secondary lymphoid follicle - in the germinal center, B cells exposed to antigens coming from the lymphatics and developed, producing antibodies, fine tuned by variable region changes. If have mistakes, will self-destroy. Susceptible to oncogene mutations which lead to lymphoma.
- Senescent germinal center - self-dissolve germinal center at the late stage.
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Peyer's patch - small bumps lining small intestine; contains _____ and _____, covered by small intestine _______ containing specialized _____ which have characteristic ________, through which they capture antigens passing by and bring them inside.
- germinal centers
- T cell area
- epithelial layer
- M cells
- membrane ruffles
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Other mucosa areas
- Gut mucosa
- NALT (nasal-associated lymphoid tissue)
- BALT (bronchus-associated lymphoid tissue)
- All arranged in similar way as small intestine mucosa.
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Thymus
- Cortex - training area
- Medulla
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Lymphocyte recirculation
Lymphatics carry lymph which takes Ags from sites of infection to draining lymphoid organs. Activated & nonactivated lymphocytes return to bloodstream, and reach sites of infection.
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Afferent lymphatics go to lymph nodes.
not the Peyer's patch
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