study notes for lecture eight: priming the T cell response

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8 Mar 2011

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adaptive immunity
Æadaptive immune response is one of antigen-specific lymphocytes (B and
T cells) to the antigen
Æincludes the development of immunological *memory
*memory: ability to respond to the antigen of the individual infected with the
same antigen
recognition mechanisms of adaptive immunity
Æslow = days to weeks
Ævariable = can handle a wide range of pathogens/antigens
Ænumerous highly selective specificities
Æimproves during the response
humoral VS cellular
ÆB cell response that makes antibodies
Æ*humoral immunity: antibody-mediated specific immunity made in a
humoral response
Æcan be transferred to unimmunized recipients by using immune serum
containing specific antibodies
Æ*cell-mediated immunity: any adaptive immune response in which
antigen-specific T cells have the main role
Æcannot be transferred to a naive recipient with serum antibody
Æfirst noted with DTH response
adaptive immune responses
Ægenerated by clonal selection of lymphocytes (1 lymphocyte sees 1 antigen)
Ædistinct from innate and non-adaptive immunity {which are not mediated by clonal selection}
Æhallmarks include
*specificity: immune responses are specific for antigenic determinants or epitopes
*diversity: vertebrate immune system has the capacity to recognize ~1015 antigens/distinct epitopes through their immune receptors (B and T cells)
*self/non-self discrimination: the immune system has the capacity to recognize foreign peptides from self peptide (autoimmunity VS tolerance)
*self limitation: immune responses are transient and tightly regulated (programmed cell death and apoptosis)
\\Ærecall what happens during a host response
Ævast majority of T cells that have undergone clonal expansion will die during the immune response and leave a small number of memory cells to circulate in the
Æat the molecular level, an antigen is characterizHGE\LWDELOLW\WREH³ERXQG´DWWKHDQWLJHQ-binding site of an antibody
*antibodies tend to discriminate between the specific molecular structures presented on the surface of the antigen
Æusually proteins or polysaccharides
Ælipids and nucleic acids are only antigenic when combined with proteins and polysaccharides
*non-self/non-microbial exogenous antigens: pollen, egg whites and proteins from transplanted tissues/organs
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*epitope: the structural component of the antigen actually recognized by an antibody and antigen receptor (the antigenic determinant)
\\Æsmall part of the antigen that the B/T cell receptor recognizes
Æmany pathogens display multiple epitopes resulting in a polyclonal immune response
*polyclonal response: response induced by multiple epitopes involves multiples clones of different specificities
polio virus
Æviral coat has 3 different proteins ± each with their own epitopes
((multi-step process of T cell activation))
Naive T cell
- has successfully made it through positive and negative selection in the thymus
- circulates the body looking for antigens but has never encountered an antigen
Activated T cell
- specific for antigen
- has received signal 1 and signal 2
- will be induced to undergo *clonal expansion (peaks at one week following antigen exposure)
clonal expansion
- T cells expand in response to infection
- some of the progeny differentiate into effector cells
- majority will die
- memory cells persist
- kinetics and number of cells are typical of the response of CD8+ T cells in the spleen of a mouse {lymphocytic
choriomeningitis virus}
- other intracellular microbes elicit qualitatively similar responses
peak/effector response
- T cells adopt an effector response
Effector T cell
- has received signal 1 and signal 2
- has expanded
- has begun to exert so-called effector function
::cytokine secretion
::killing of infected target cells
- T cells go to the areas of infection
- once T cells have exerted their effector function, the vast majority will die
- leaves a small number behind
Memory T cell
- has been activated by antigen
- has undergone clonal expansion
- has exerted effector function
- remaisn after the contraction period
- can respond very quickly and robustly to re-infection with the immunizing antigen
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dendritic cells
Æmost potent antigen-presenting cells
*skin and mucosal tracts {airways, gut, reproductive tracts} are vulnerable to infection because they are exposed to the environment
Æin an uninfected person, are relatively sessile and do not migrate around ± their dendrites are good for feeling around for antigens
Æin an infected person, those that have acquired antigen, leave the tissue beds and enter the lymphatics that transports them to the closest lymph node
1) dendritic cells capture foreign antigen in a site {ie: skin}
2) dendritic cells leave the skin via AFFERENT LYMPHATIC SYSTEM
*afferent lymphatics: point of entry into the lymph node
*it is within the lymph node that T cells and dendritic cells first interact
3) dendritic cells bearing antigen enter the lymph node and prime a naive T cell
4) naive T cells that receive signal 1 and signal 2 divide (clonal expansion) and differentiate
5) after undergoing several rounds of division, antigen-VSHFLILF7FHOOVDUPHGZLWK³HIIHFWRUIXQFWLRQOHDYHWKHO\PSKQRGHYLD())(5(17/<03+$7,&
6) antigen-specific effector T cells go to the initial site of antigen encounter to fight the infection
scenario A
Æin a resting APC it is deficient in a co-stimulator
Æantigen recognition is only recognition of a self-antigen = only signal 1
ÆMHC²peptide and co-receptor (CD4 or CD8) interact but no CD28 signal
= T cell can see self-antigens
\\Æin most cases, without a signal 2, the T cell will die
scenario B
Æactivated APCs have increased expression of co-stimulators allows for
secretion of cytokines
Æantigen recognition of antigen and B7 {inflammation signal} = both signal
1 and signal 2
Æthere is enough inflammation that the antigen-presenting cell displays B7
which interacts with CD28
Æthis activates T cell proliferation and differentiation
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