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35 Cards in this Set
- Front
- Back
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What is the major histocompatibility complex? |
region formed by the genetic loci involved in rejection of foreign tissue
central in humoral and cell mediated (adaptive)
40-50 genes in chromosome 6 |
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What are the classes and distinctions of MHC complexes |
Class I and II represent distinct structure entities that exhibit similar overall structures
Class III contains a diverse collection of ver 20 genes for complement and antigen processing |
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What are the class I types |
A B and C
bind endogenous Ag on nucleated cells |
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What are the distintions in Class II |
DR DP and DQ
bind exogenous Ag on Ag presenting cells |
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What are the class III distinctions |
serum soluble proteins
C4 C2 Bf |
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What are unique features about the MHC loci |
highly polymorphic, with many alt. forms of the gene or alleles
CODOMINANT EXPRESSION from each parent |
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What is the structure of Type I MHC molecule |
alpha chain and a beta 2 microglobin with the alpha chain encoded by ABC regions on HLA
found on membranes of all nucleated cells |
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What is the structure of the MHC II molecule |
2 polypeptide chains an alpha and beta chain
both chains are encoded by the D region of HLA
found on certain immune system cells |
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What is the structure of MHC III |
are soluble proteins
have no membrane bound regions
play no role in Ag present |
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What is the role of MHC polymorphisms in disease and transplant |
wide range of alleles makes matching donors for transplants and many disease may act on MHC alleles (autoimmune or allergies eg)
A pathogen may alter the role of MHC in immune response, mimic the MHC alleles or bind to MHC binding sites |
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What is antigen processing? |
essential cellular and biochem events that activate CD4 and CD8 T cells after an acessory or APC binds an antigen |
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What are the principles of antigen recognition: abs and B cells |
usually antibodies bind to a conformational aspect of the antigen
B cells that produce the Igs to the originial natural form of the antigen therefore it must be in its NATURAL state to be recognized before the antigen is processed |
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How do T cells recognize antigen |
T cells recognize the denatured or native molecules that have already had the opportunity to undergo biochem rxns
Usually small linear sequences of at least 10-12 aminos |
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What are the characteristics of T cell lymphocytes; CD4+ |
helper T cells
recognize antigens in association with class II MHC molecules
CD4 acts as a receptor for MHC Class II molecules |
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What are the characteristics of CD8+ cells |
cytotoxic T cells
recognize antigens in response to Class I MHC molecules
is the receptor for the antigens expressed by MHC I molecules
kill the cells that present |
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CD4 and APC processing |
APC cells must uptake the antigen then alter it to the point where it can be recognized by CD4 and be presented using the MHC II system
CD4 can present their own molecules but the body has mechanisms to prevent self recognition |
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Steps to CD4 recognition |
APC takes up Ag
APC alters Ag
Ag is placed on MHC II
Expression of molecules that stimulate the growth and differentiation of CD4 cells |
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What are the major APC all class II |
Macrophages
B cells
Dendritic cells |
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Describe macrophage uptake. |
Have receptors for carbs, Fc portion of antibodies, C3 complement
MAJORLY TARGETED to OPSONIZED ANTIGENS |
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Describe B cell uptake? |
preferentially take up antigens that bind to specific Ig receptors |
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Describe dendritic cell uptake |
most important APC
receptors for glycoproteins carbs and TLRs |
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What is the mechanism of antigen processing |
Protein antigen is taken up and digested by acidic intracellular vesicles
after being processed the fragments are presented on membrane via MHC II |
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What is the relationship of MHC-antigen association |
Greater the binding the greater the immunogen
With greater association the T cell can respond better and a greater immune response generated |
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What are the characterisitics that confer binding to the MHC |
follows common chemical motifs such as charge hydrophobicity etc.
MAJOR factor is side chain configuration such that it can fit the grooves of the MHC molecule
This association occurs in specific intracellular organelles |
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Where and how does the association of the MHC peptide occur |
Antigens are cleaved by cytoplasmic proteases then transported to the RER
In the RER Class I and Class II are synthesized and assembled with the peptide then associating for presentation |
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How do the peptide antigens get into the RER? |
ABC proteins transport SPECIFIC peptide sequences into the RER (TAP-1 and TAP-2)
where they then combine with the MHC |
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How is antigen presented to CD8 cells |
requires stronger secondary signals then CD4 activation
some evidence may suggest activation of CD8 cells may require CD4 cells to recognize the same endogenous antigen on the APC
CD4 cells signal increase the co-stimulatory activity of the pathogen infected APC |
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What are the differences between Class I and II |
Class II chains reside in the RER and are complexed to an additional component called the invariant chain
this complex is moved to the lysosome where the invariant dissociates and the antigen peptide replaces it |
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Class I and II diff cont. |
***Following RER synthesis both Class I and II antigens are transported to the Golgi comp.
Class I and II segregate with I going to the cell surface and II arriving in the lysosomal compt. |
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Transmembrane Transport of Class II complex |
antigenic peptide is again swapped for an invariant chain in the class II complex resulting in the class II-antigen peptide being transported to the cell surface
one more step of the lysosomal process |
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How are MHC Class II molecules managed |
the quantity on monocytes and macrophages varies
interferon gamma released by T cells during antigen present binds to receptors on young phagocytes causing an increase in type II |
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Antigen recognition and T cells |
has both receptors for the complex and the specific antigen |
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What are the interaction molecules |
Other molecules are responsible for bringing T cells to APCs
CD4 is a ligand for Class II MHC with a role in cell-cell adhesion as well as signal transduc
CD8 ligand for MHC I |
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What are the major T cell and APC cell interacting molecules |
T cell: CD4/8/2 LFA-1
APC surface molecules: ICAM-1 and LFA-3 |
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What are the role of superantigens in the antigen present pathway |
Produced by pathogens from bacteria to retroviruses
bind to both MHC class II and TCR simultaneously
Stimulate most T cells that express a given alpha/beta sequence
They are not processed into peptides and do not bind the normal MHC molecule site |
