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70 Cards in this Set
- Front
- Back
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what is the cause of hyperacute graft rejection?
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preformed ABO antibody to endothelium
occurs within minutes |
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what are the three means by which allograft MHC can account for rejection?
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1. graft MHC presents host peptide to Host T cell
2. graft MHC presents graft self peptide to host T cell 3. host APCs take up graft MHC and other peptides activating host immune response |
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what is primary (first set) and secondary (second set) allograft rejection?
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primary: 11 hours.
secondary: 5 hours both caused by cytotoxic T cells |
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what are the minor histocompatability proteins?
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functional proteins that are variable in structure but not in function. hypervariable at a couple non-fx AAs
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how can you suppress graft rejection by T cells?
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give an anti T cell Ab (anti CD3
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what are the effects of hyperacute graft rejection?
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complement fixation on graft endothelium, thrombosis
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what is the theory of the cause of chronic graft rejection and how can you diagnose it?
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the theory is that it is mostly Ab events. It results in scarring which can be seen on biopsy
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what are the main pharm tx for tissue transplantation?
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CYCLOSPORIN (blocks signal 2)
anti t cell Ab (anti CD3) steroids |
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what population is at high risk for tumor malignancy?
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patients with autoimmunity
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what is the difference between tumor specific Ag and tumor associated Ag?
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tumor specific: only expressed on tumors
tumor associated: expressed in much higher levels on tumors than normal tissue |
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why is giving a bladder infection helpful for patients with superficial bladder cancer?
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it upregulates APC activity, increasing the likelihood of presenting tumor Ag
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what are the 5 ways in which tumors can evade immune response?
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1. tolerance
2. antigenic modulation 3. antigen shedding 4. downregulation of MHC I expression 5. secretion of immunosuppressant molecules |
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what tissues have mucosal immune system?
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any epithelia that has exposure to the environment (besides the keratinized skin)
resp, GI, urogenital, mammary |
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how is the general job of the mucosal immune system different than the general immune system?
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you have to generate tolerance to food Ag and to commensal bacteria
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does the liver have MALT?
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no
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what is Waldeyer's ring?
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the ring of MALT at the back of the mouth. Adenoids flank the uvula, palatine tonsils are in the arch, and lingual tonsils in the tongue
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what are Beta-defensins?
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amphipathic (hydrophobic and hydrophilic parts) molecule secreted by mucosal epithelium tha tcan break down membranes of pathogens (and even self)
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what types of cytokines increase the permeability of mucosal epithelial tight junction barrier?
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inflammatory cytokines
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what cytokines DECREASE the permeability of the mucosal epithelial tight junction barrier?
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TGF-beta and IL-15
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what is the function of Beta defensins?
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made by mucosal epithelium
induce cytokines and guide the inflammatory response |
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paneth cells make what type of defensin?
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alpha-defensin
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what are the two types of cytosolic PRRs in the mucosal immune system?
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the retinoic acid inducibles (RIG) and the NOD/NLR group
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what TLRs are expressed in mucosal epithelium?
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TLR2, TLR4, TLR5
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TLR5 is expressed on what surface of the mucosal epithelium?
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on the apical side...so only things that can get through can stimulate TLR5
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what are the downstream effects of TLR binidng in the mucosal epithelium
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TLR binding
increased NF-kappa B increases synthesis of pro-IL-1 (pro-IL-1 is IMPORTANT) |
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NOD1
when is it expressed? what does it lead to production of? |
expressed constitutively
increases beta-defensin |
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NOD2
when is it expressed? what does it lead to production of? |
induced by TLR signalling
increases alpha-defensin |
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what is the function of pro-IL-1
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it is required to turn on the inflammatory response in the mucosal epithelium
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what is the function of NALP1 and NALP3?
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they are PRRs, they turn pro-IL-1 to IL-1
turning on the inflammatory response |
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what is pyroptosis?
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induced cell death in response to an inflammatory response
it can provide a signal of inflammation |
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what is the role of autophagy?
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the ability of the epithelium to phagocytose other areas of infected epithelium
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how are commensal bacteria tolerogenic?
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they lead to production of thymic stromal lymphopoeitin
when there is also Retinoic acid and PPAR-gamma the resident DC are guided to direct T cells toward Treg differentiation |
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how do you get NK cell killing of infection mucosal epithelial cells?
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infection induces expression of MIC
NK cells have NKG2D receptor which binds the MIC and kills the cell |
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what is the immune function of goblet cells?
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mucin secreted traps microbes and trap pathogens which are moved out by ciliary mov't
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what is the function of TGF-beta
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differentiation of Tregs and for isotype switching to IgA
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what is the function of intraepithelial CD8 lymphocytes?
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they secrete TGF-beta
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what is the function of M cells?
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they are in line in the mucosal epithelium
have a cleft where lymphocytes or dendritic cells can fit and take up antigen |
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what are the main signals that predispose for the development of Tregs?
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retinoic acid and conditioned Dendritic cells
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what is the "marker" name for Tregs?
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CD4, CD25, foxp3 cells
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how do Tregs suppress inflammation?
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through cell-cell contacts
production of anti-inflammatory TGF-beta uses LOTS of ATP (bc atp is an inflammatory signal) |
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what is the function of a Th17 cell?
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it takes over inflammation (overcomes Treg) during a necessary inflammatory response in the mucosal immunity
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under non-inflammatory circumstances, what cells are in the interstitium under the mucosal epithelium?
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all lymphocytes and leukocytes except for neutrophils
the mucosa is primed for an inflammatory response |
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what 2 signals favor secretion of IgA in the mucosal epithelium?
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TGF-beta and APRIL (a TNF-alpha family member)
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if a lymphocyte is activated in the GALT, how do they go back to the gut?
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through the action of gut homing receptors
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what are the main gut homing receptors?
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CCR9
alpha4beta7 downregulation of CCR7 and L-selectin |
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how are gram-negative bacteria particularly important for the formation of GALT?
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they bind NOD1 to induce development of GALT
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how does bacteroides thetaiotaomicron sidestep the mucosal immune system?
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it induces PPAR-gamma (anti-inflam) which blocks NF-kappaB signalling so you get less pro-IL-1
DECREASES inflammation |
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what is the cause of Inflammatory Bowel Disease?
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failure to control immune response to commensal flora
balance tipped toward Th17 and away from Treg |
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how are commensal flora therapies being used for crohn's disease and ulcerative colitis?
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giving microbe that is non-harmful in man which induces a favorable development of Tregs
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what are the 4 most common sources of allergens?
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inhaled
ingested injected contacted |
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how does type I hypersensitivity rxn happen?
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there are preformed IgE
when Ag is present, mast cell Fc receptors bind the IgE and degranulate (histamine, TNF-alpha.etc) |
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what are the contents of mast cell granules and which hypersensitivity type are they important in?
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Type I hypersensitivity
Histamine TNF-alpha IL-3, IL-5, GM-CSF (eosinphil activation) leukotrienes (mucous secreiton, SMC contraction) |
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how do mast cells participate in 2 positive feedback loops in Type I hypersensitivity rxns?
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mast cells express CD40L and also IL-4, thus providing help for B cells to produce MORE IgE in response to mast cell Fc receptor binding the IgE-Ag complex
they also activate eosinophils, and eosinphils activate more mast cells |
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how are eosinphils invovled in Type I hypersensitivity rxn?
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activated mast cells activate nearby eosinophils, so the eosinophils can bind the IgE-Ag complex, leading to eosinophil degranulation
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what are the contents of eosinophils?
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collagenases
major basic protein - triggers mast cell degranulation IL-3, IL-5, GM-CSF (more eosinophil produciton) |
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how does nickel lead to type IV hypersensitivity rxn?
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it cross links TLR4 (takes the place of LPS) with MD2
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why do people have dust mite allergy?
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dust mite allergen (der p 2) looks like MD2
lung normally doesn't have MD2 thus, when you inhale LPS, der p 2 takes the place of MD2 and you get TLR4 signalling |
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why do some people develop type I hypersensitivity?
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increased IL-4 production by Th2 cells leads to lots of class switching to IgE
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what is the main common problem of autoimmunity?
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failure of T cell tolerance
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how can you get autoimmunity to eye or testes?
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they are normally immune privileged. if you get trauma, the barrier can be broken down, and then immune effectors can infiltrate the eye to which they are normally not exposed
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how can MHC II be involved in autoimmunity?
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MHC II is upregulated in some inflammatory states, presenting self antigen to CD4 T cells
this can especially happen at the thyroid |
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what is the most common cause of autoimmunity?
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insufficiency of Tregs (CD4, CD25 foxp3 cells)
(lupus, diabetes, MS) |
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how can molecular mimicry lead to autoimmunity?
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pathogenic Ag looks like a self antigen, thus creating a BCR or TCR that is reactive to self
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what is "herd immunity"
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immunity in a high enough percentage of the population that disease in a couple people will not spread
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what is necessary to be able to eradicate a disease?
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can't be transmittable to animals
obvious clinical manifestation (to identify people who do get it) few strains, not much genetic drift (so the same vaccine works for decades) |
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what type of vaccine induces CD8 CTL response?
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live attenuated vaccines
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how can you make a subunit vaccine more effective?
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add adjuvants: molecules that augment the immune response (cytokines, TLR ligands), or adjuvants can increase antigen half life
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what are the only 2 adjuvants approved for subunit vaccines
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aluminum hydroxide: helps prolong halflife
ASO4: activates TLR4 |
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what are the worst immunogens?
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polysaccharide vaccines
they are T-cell INDEPENDENT IgM only |
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how can you successfully immunize against polysaccharide Ag?
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conjugate a protein antigen to it for the T cells to recognize
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