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92 Cards in this Set

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Define: Exogenous antigen processing pathway
denaturing of protein and glycoprotein antigens derived from either endosomes or phagosomes and degrades them into small polypeptides.
What happens to the polypeptides formed from the exogenous antigen processing pathway?
They are loaded into HLA Class II molecules and transported to the surface of the cell for presentation to CD4+ T helper cells in order to activate them
Define: endogenous antigen processing pathway
uses polypeptides derived from the cells own protein synthesis machinery
What happens to the polypeptides formed from the endogenous processing pathway
they are loaded into HLA Class I molecules and transported to the cell surface for presentation to CD8+ cytotoxic T cells in order to activate them
What is genetic polymorphism
each gene for and HLA molecule can have multiple stable forms or alleles within a specific species (structure remains the same, but amino acid sequence will differ)
Describe HLA class I molecules
Monomer consisting of three domains (alpha 1,2,3). CD8 binds to alpha 3
Describe HLA class II molecules
Dimer consisting of an alpha and beta chain. Similar to class I molecules. CD4 bind to beta 2 domain.
Describe the exogenous antigen processing pathway in detail
1. phagocytosis or endocytosis causes antigens to be denatured/degraded
2. HLA class II molecules and a protein called INVARIANT CHAIN are synthesized
3. Vesicles with HLA class II and li are fused with phagolysosome or edosome.
4. Peptide exhange occurs
5. Vesicles fuse w/ golgi or are loaded into HLA class II peptide binding grove
6. complex interacts with CD4+ cells
7. Activation of CD4
What purpose does the invariant chain (li) serve in the exogenous antigen processing pathway (2)
1 stabilized unbound HLA class II molecules while they are being synthesized
2. blocks accidental binding of endogenous antigens
Describe the endogenous antigen processing pathway in detail
1. Processing of endogenous antigen (ie proteins made my viruses and tumors)
2. Ubiquitin is attached to targeted antigens for destruction
3. Proteasomes degrade ubiquitin-protein complex
4. Resulting peptide fragments trasported to rough ER
5. In ER they bind to HLA class I alpha 1 & 2 domains
6. peptide fragments are loaded into HLA class I binding grove.
7. HLA class I - peptide complexes form.
8. Transported to golgi where they are recognized by CD8+ cells
8. CD8+ activated and kill
What does it mean when Mature T lymphocytes are "HLA restricted"
they recognize foreign antigens only if they are presented to them in association with a self HLA molecule
What are Th1 cells mainly do
they positively influence cellular immune responses
What do Th2 cells mainly do
they upregulate antibody response
What three things happen in the thymus in respect to maturation of T cells
1. aquires the T cell antigen receptor (gains antigen specificity)
2. learns self tolerance
3. learns self-HLA restiction (recognition of foreign peptide only in association with self HLA Molecules
Explain how a T cell reconizes a foreign antigen
T cells become activated when the immunological synapse is formed between an APC(antigen presenting cell) and a T cell.
What t cells can mature without a thymus
γ/δ+ TCR
Describe whas CD3 does (2)
1. its a chaperone for TCR (transports newly synthezied TCR molecules to the cell surface)
2. Functions as a cellular signaling molecule
What happens after there is activation of T helper cells (what IL factor
IL-2 and Il-2 receptor genes are trascribed
What does IL-2 induce
proliferation of T cells which leads to effector cell function (production of cytokines) or antibody production
HOw is binding of HLA and the associated processed peptide to the TCR stabalized
by coreceptors CD4 and CD8
What do Th1 cells produce after activation
IL2 and interferon gamma
what do Th2 cells produce after activation
IL4 IL5 IL13
What IL factor is there an absolute requirement for in order to signal CD8 to proliferate and differentiate into CTL effectors
IL2
Granule mediated killing
T cell attached to target cell via HLA class I with TCR interactions. Granules are aimed at target.

Apoptosis - programmed cell death.....granzymes are released and internatlizes through perforins.
What is a major player in the granules during granule mediated killing
perforin. This binds to the target membrane and polymerizes in the presence of Ca2+ to for transmembrane channels, this increases cell permeability. Causes cell death
How is apoptosis regulated
Tumor necrosis factor beta and alpha both induce apoptosis.
What is released during apoptosis in to the target cell
granzymes. play a role in cell lysis
what is an example of a granzyme
fragmentin.....induces DNA fragmentation and apoptosis
Explain Fas-FasL ligand killing mechanism
cell surface molecule called Fas ligand (FasL) on the CTL bind to Fas on the target cell. This activated enzymes called caspases in the target cell and induces apoptosis.
What happens after the lethal hit in apoptosis
CTL detaches and moves to the target and potentially kills man more target cells before dying itself
What are NK cells classified as
large granular lymphocytes
What is another name for NK cells
CD56/CD16
Do NK cells require prior sensitization, immunization, or antigen presentation via HLA to kill their targets
NO
DO NK cells have memory
NO...they are part of the innate immune response
Describe how NK cells recognize and kills
1. recognize a lack of MHC expression (lack of self)
2. NK cells have killer cell inhibitor receptors (KIR's)
3. WHen MHC expression is down regulatioed, KIR receptors are not engages on the NK cell and the cell target is lysed
3.
What do NK cells release to kills
perforins and granzymes (although slightly different in appearance to T cell perforins)
What can NK cell activity be upregulated by?
IL2 and IFN gamma (NK cells also produce IFN gamma)
What activates macrophages
interferon gamma
What kind of radicals are produces my macrophages
nitrogen and oxygen
antibody dependent cellular cytotoxicity...what makes NK Cells good at this
NK cells are especially good at this, Their CD16 surface markers is a receptor for the Fc region of the IgG
What other cells, besides NK cells, are good at antibody dependent cellular cytotoxicity
cells must possess CD16 and function as K cells for ADCC. monocytes/macrophages, eosinphils, neutrophils, and CTL
What occurs with cells that have antibody dependent cellular cytotoxicity (ADCC)
THey bind to pathogens, tumor, or cirus ingected host cell via specific antibody and then become cytotoxic
Define Autographt
is a graft or a transpland from one anotomical location to another on the same individual. NO DIFFICULITES WITH REJECTION
Define isograft
graft or transplant from one individual who is syngeneic to the donow. Donor and recepient are HISTOCOMPATIBLE. no rejection expected
Define Allograft
graft or transplant from one individual to a genetically dissimlar individial of the same species....rejection expected
Define Xenograft
graft between a donor and recepient from different species...graft will be rejected
Describe hyper acute graft rejection
1.Occurs within a few hours.
2. Caused by preformed antibodies to incompatible MHC molecules and activation of the complement cascade. Cell mediated immunity is not involved....


antibodies are already present at the time of transplantation

no therapy for this
Describe acute graft rejection
Begins within a few days
Caused by T cell mediated immunity and is a result of mismatch or incomplete match in HLA types between recepient and donor.
Destruction is caused by CD8, CD4, and phagocytosis.
Describe chronic graft rejection
Occurs months or years after transplant.

Initially caused by activation of CD4 cells, followed by activation of other factors.

Mechanism is caused by lymphoid proliferation and formation of lymphoid follicles in the transplanted organ which causes scarring
Describe (Graft vs host) disease
Seen comomonly in bone marrow transplant. Transplantation of lymphocytes from a genetically dissimilar donor cause donor lymphocytes to mount an immune response against the recipients tissues. Transplanted lyphocytes must be immunocompotent and recipient must be immunosuppressed.
Name the three MCH class I linked genes (loci)
A, B, C
Name the three MHC class II linked genes (loci)
DP, DQ, DR
What do the linked genes or loci allow for.
a great number of variations
IF there is no processed peptide what initiated a graft rejection?
HLA class II molecules
What is the key initiating event in acute allograft rejection
direct activation of recepients CD4 T cells by NON self HLA class II molecules expressed on the grafted tissue
What are the most potent transplatation antigens
HLA class II Molecules
What are important cytokines in allograft rejection (Th1 or Th2)
Th1.....graft rejection reflects a type 1 immune repsonse.
Lymphocytotoxicity test
commercially prepared antibodies of known specificity against human HLA antigens are added in the presence of complement with donor or recepient cells. Lysis or damage of cells idetifies presence of that specific HLA antigen
Genotyping of HLA molecules by PCR
detects more refined differences in HLA
Detection of transplantation antigens by MLR
Takes 4-5 days....Useful if transplantation is from a living donow because it can indicate the degree of parity between the donor and recepient...it mirrors the reaction that would occur invivo
Why cant MLR be used to test the organ and recepient using a cadaver.
By the time the test is completed the organs will no longer be viable
Two way MLR
leukocytes from the donor and recipient are mixed together. If the recipent or donow recognizes foreigness they will resond and prolifereate. After three days, radioactive material added...there is a direct correlation between radioactive material incorporated and proliferation. This predicts the liklihood of a rejection
One way MLR
Test to see if the recipients leukocytes will respond against donor HLA antigens. Mitomycin C treats the donor cells. Only viable recepient cells will now respond.
What does monocolonal orgin mean and what orginated this way
arises from a single cell. Cancer
what is p53
tumor suppressor protein
If a cell has damaged DNA what does p53 causes
apoptosis
Lymphokine activated natural killer cells (LAK)
obtained from peripheral blood of cancer patients. Grown in presence of IL2 and then transfused back into patient in combination of IL2. Unsuccesful
Tumor infilitrating lymphocytes
NK cells and some T cells grown in prescense of IL2. Injected back into patient with IL2. Unsuccesful
What does it mean to be located in an "immunologically privileged site"
tumors in these areas are not subjected to certain immune components and surveillance mechanisms

eye brain skin gonads
What kind of immunity combats pathogens and toxins in the extracellular environment
Humoral immuninty and phagocytosis
What kind of immunity combats pathogens in the intracellular environment
antibody and cellular immunity (t cells)
What is an example of an obligate intracellular pathogen
virus
What are the first responders in innate immunity
phagocytes and alternative complement pathway activation
In order for a pathogen to survive within phagocytic cells waht must occur (5 things)
1. pathogen actively inhibits phagosome-lysosome fusion
2. escape the phagolysosome and reside in the cytoplasm
3. be resistant to digestion with in the phagolysosome
4. become latent within host cells
5. steer the immune respone to an ineffective one (Th1 -> Th2)
alpha and beta interferons find to their cellular receptor and induce a resistant state within host cells. What are 4 characteristics of the antiviral state
1. Decrease membrane fluidity, precents pathogen penetration and release from host cell
2. production of enzymes which destroy viral nucleic acids
3. inhibition of pathogen protein synthesis
4. increase in HLA expression enhancing recognition by CD8 cells
What do interferons act on
Host cells only
What produce gamma interferon and when
1. CD4 Th1 cells during adaptive immune responses
2. NK cells in the innate response
3. CD8 cells during adaptive immune responses
What two things combine synergistally to activate macrophages
interferon gamme and tumor necrosis factor alpha (TNF alpha)
What 4 things to activated marcrophages cause
1. Respiratory burst activty (more free radicals are created that are highly toxic)
2. Increased O2 independent killing mech
3. Increased HLA expression which leades to enhanced antigen presentation
4. Increased density of receptors for opsonins such as C3b and Fc (these increase phagocytosis)
In order for CD8 CTL activation to occur, what must occur first
CD4 Th1 cells must be activated
What do CD8 cells require to become fully active? (cytokine)
IL2 from CD4 Th1 cells
In helminthic parasite infections what immunogloblin is produced
IgE...this could lead to a reaction that mimics allergies
Do helminth antigens induce Th2 or Th1 cells, which do they suppress
Induce Th2 and suppress Th1
What interleukin factors are suppressed and stimulated in a helminth infection
stimulated IL4 IL5 (Th2 cytokines)
supressed Il2 gamma interfon (Th1 cytokines)
What is a strong inducer of IgE synthesis
IL 4
what stiumlates eosinophil growth and differentiation
IL 5
WHat kind of toxins are produced by gram negative bacteria, gram postive bacteria
Gram negative - endotoxins and exotoxins
Gram positive - exotoxins
At what concentraion are exotoxins active in causing disease
At very low concentration that are not neccesarily immunogenic
What three things do endotoxins induce
IL1
TNF alpha
IL6

all inflammatory cytokines
What pathway do endotoxins activate
alternative complement pathway
From which, an endotoxin or an exotoxin, can a toxoid (vaccine) be formed
exotoxin. endotoxins have multiple anitgenic types and cause little to no acquired immunity
What are 8 examples of vaccine containing whole organisms
1 pertusissis
2 rabies
3 hepatitis A
4 intramuscular poliovirus
5 influenze
6 plague
7 cholera
8 paratyphoid fever