TAP
peptide transporter that delivers processed, endogenous antigen in to the ER to be complexed with MHC I
polymorphism
refers to population level
polygeny
refers to individual level
microbial superantigens
bind MHC II Class outside of normal binding groove; can cause activation of huge # T cells (10%); nonspecific binding therefore broad activation by binding multiple TCR via b chain, cytokine storm, sepsis
is memory generated against microbial super antigens?
no , T cell activation is inappropriate so no mem developed
do microbial superantigens require processing?
no
ankylosing spondylitis
B27
HLA DQ2 DQ8
diabetes type I and also celiac
abacavir
drug used in HIV tx that can cause hypersensitivity in indv with HLA B 57 by changing the peptide binding characteristic of MHC II
Carbamazepine
anti epileptic that can cause hypersensitivity in HLA B 15
calnexin
keeps MHC I alpha stable until B2 binds
calreticulin (a chaperone)
keeps MHC I a:b2 stable until TAP bind s
polymorphism
population level
polygeny
individual level
what c’some are MHC I and MHC II genes on
6, with the exception of b2 which is on 15
Peptide anchor residues
mediate binding to MHC; side chains of aa residues of peptide that fit into pockets of peptide binding cleft of MHC; peptides that can load a particular MHC are similar in their gene seq, and pretty conserved
IL2R alpha chain
CD25
IL2-Receptor
present on naive T cells, B cells, NK cells, activated T cells
what pathway does cyclosporin A target
TCR-CD3 signaling (by targeting calcineurin calmodulin calcium phosphatase activity)
what can cause SCID besides a RAG1 or RAG2 mutation?
deficiency in gamma subunit of the cytokine receptors
class I cytokines
2,4,6,12
class II cytokines
IFN receptors , IL10
IFN alpha and beta
antiviral
IFN gamma
macrophage killing, MHC II expression, antiviral responses
thymic aplasia
Di George syndrome; no T cells , dcr PTH dir Ca
ex of killed or inactivated vaccine
RIP Always (rabies, influenza, polio, hepA)
what attenuates immune response
both TGF Beta and IL10
which hypersensitivities are ab mediated
I, II, III
things required for class switching
happens in germinal centers, requires antigen and MHC and T cell (therefore, requires CD40L - present on T cells, without it can get hyper IgM )
what kind of signaling does class II cytokines use?
JAK/STAT
JAK kinases
kinases involved in immune response(inhibitors tune down the T cell response)
pre TCR complex
following successful rearrangement of B chain for TCR, betaTCR:pTa:CD3 complex signals for stopping beta rearrangement (allelic exclusion), stimulation of proliferation and CD4 CD8 expression, stimulation of alpha chain rearrangement
Homeostatic proliferation
t cells in the periphery proliferate (this is why we still have T cells despite our thymus involuting)
B7
on APC; binds CD28 on T cells
pleitorpy
acts on more than one target
redundancy
multiple cytokines act on same cell for the same effect
synergy
two cytokines work together to produce a given effect
antagonism
one cytokine undoes the action of another cytokine
whats secretes IL1
macrophages
phases of DTH
sensitization and effector
cd40
present on B cells
present on macrophages
therefore without CD40L, T cells can’t communicate with either
RORyT
expressed by Th17
FoxP4
expressed by Tregs; without it, get IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X linked)
induced t reg function
down regulate immune response; generated in periphery
innate t reg function
maintenance of self tolerance; generated in thymus
Bcl6
expressed by TFH
Follicular helper T cells
TFH; express Bcl6; secrete Il21, express ICOS ; help B cells during germinal center reaction (class switching and somatic hypermutation)
CXCR5
expressed by resting B cells
CCR7
expressed by resting T cells
major killing pathway for CD8+ cells
perforin/ granzyme mechanism
minor killing pathway for CD8+ cells
FAs ligand to induce apoptosis
what is the common end point of perforin/granzyme and Fas pathways
activate procaspase into caspase which can activate apoptotic factors
type 1 hypersensitivity
IgE, mast cell activation, soluble antigen, systemic anaphylaxis, acute urticaria, seasonal rhinoconjuncitvitis, asthma and food allergy, asthma
type 2 hypersensitivity
IgG, cell or matrix associated antigen; FcR cells = phagocytes, NK cells; complement
what kind of rxn is against penicillin
type 2 hypersensitivity
what kind of rxn is against TB
type 4 hypersensitivity
what type of hypersensitivity is for serum sickness
3
what type of hypersensitivity is for arthus
3
what do type I II and III hypersensitivities have in common
all are antibody mediated
what kind of reaction is poison ivy
type 4 CTL mediated hypersensitivity
what kind of cell will bind IgE
mast cell!!!
why is it that upon first exposure of antigen nothing may happen?
because during sensitization you create the antibodies (IgE) that can bind to the mast cells. But just the IgE binding to the mast cell does not trigger degranulation; it is the mast cells expressing IgE that then come in contact with the specific antigen that will cause degranulation; this is also why if you are developing an anti-IgE antibody to mediate allergic rxns you need to be only targeting soluble IgE because if you cross link the IgE thats already bound to the mast cell then you will actually promote degranulation and anaphylaxis
can mast cells secrete interleukin?
yes they secrete Il4 which amplifies IgE production
name as many things as you can that mast cells can release
histamine heparin tryptase carboxypeptidase cathepsin Il4 Il13 Il3 Il5 GMCSF TNF alpha CCL3 prostaglandins leukotriene platelet activating factor
what can present haptens
haptens need carriers; can be taken up by langerhans
tissue transglutaminase
modifies gluten so that it can bind MHC II –> celiac (activated CD4+ cells can bind FAS and kill epithelial cell
FUT 1 mutation
no H antigen; bombay phenotyp
FUT 2 mutation
80% ofpeople have polymorphism that causes presence of ABO in secretions
Intravascular hemolytic transfusion reaction
IgM complement fixation
Extravascular hemolytic transfusion reaction
IgG phagocytosis
isohemagglutinins
naturally occurring IgM antibodies to A or B antigens
ABO typing
erythrocytes are typed for their ABO antigens
reverse typing
serum is typed for its ability to agglutinate erythrocyte of various blood groups
test results in hemolytic disease of new born
positive direct and positive indirect coombs test
indirect coombs test
detects circulating antibodies and is typically performed on the serum from the mother.
direct coombs test
detects antibodies which are already found on the surface of the erythrocytes and is typically performed on the red blood cells of the foetus or the newborn.
glucuronidation
how to make bilirubin more excretable; in newborn’s this is generally less efficient and so bilirubin tends to accumulate more than in adults (newborn jaundice is not uncommon)
BBB of newborn
more permeable
kernicterus
brain damage due to excess bilirubin in the brain
bilirubin
degradation product of hemolysis
hemolytic disease of the newborn
IgG antibodies form mom cross placenta and react with Rh+ fetal erythrocytes causing extravascular hemolysis!!! especially in spleen; anemia, jaundice, kernicterus
bili light
phototherapy that involves exposure of baby to blue greenn light spectrum to convert bilirubin to water soluble isomer to promote excretion
how does IFN gamma activate macrophages
inducing iNOS
w/o macrophages what kind infection susceptible to?
myobacterium
what phosphorylates ZAP 70
Lck
what process is ZAP 70 involved
TCR:CD3 signaling pathway –> NFAT activation and IL2 production for T Cell stimulation and proliferation
what interleukin can promote antibody production
Il4
what immunoglobulin is important in parasite infection
IgE
TDAP vaccine
tentanus, diphtheria and pertussis
what can measles bind
binds to a regulator of the complement system
Tetanus Immune Globulin (TIG)
recommended for tetanus treatment and prophylaxis against tetanus following injury in patients whose tetanus immunization is incomplete or uncertain.
why do you not give TIG to immunized patients?
spores need to germinate, which takes time, so by the time the secondary response kicks in (2-3 days ) its still soon enough to be before the spores germinate
how many doses is MMR vaccine
2
oral polio virus
live, attenuated
polio shot
killed virus
measles shot
live, attenuated
Thimerosol
mercury based preservative, helps prevent growth and spread of bacteria; human body can easily clear thimerosol. Furthermore, the amount is so small, that, in conjunction with the rapid clearance from the body, never builds up!
what vaccines are contraindicated in peds onc patient
live, attenuated; MMR and Varicella (chicken pox)
Varicella
chicken pox
how long does passive immunity last
3-6 mo
how do you decide whether to give an HIV patient a vaccine?
depends on CD4 count! <200 do not give
what is chronic rejection characterized by
reactions in vasculature of the graft; often see inflammation that thickens vessel, therefore narrowing lumen and causing loss of function