Flashcards in Week 4 Deck (63):
INF gamma and MHC
Signal causes proteosome to switch to an immunoproteosome which leads to proper size, charge for MHC presentation
Tap 1 and TAP 2 are transport proteins which spans across the RER membrane. Affinity for proteins 8-16AA long.
ER amino peptidase. breaks up peptides down to 9 AA long. Anything smaller is further broken down to AAs.
Is present in virally infected cells. Induced by INFy and TNFa. degrades and presents viral proteins via MHC class1
MHC class II Structure
Trimer made of Alpha, beta and invariant chains. The invariant chain assists in foldin of a and b chains, binds to the peptide presenting site of the class II molecules and assists in transport from MHC class II from the golgi to the cytoplasmic vesicles. Invariant chain is cleaved to CLIP before being exchanged for antigenic peptide and presentation.
has a mutationin superoxide dismutase
enzyme which absorbs free radicles from lipid peroxides, needs selenium.
alpha tocopherol. Most widely distributed antioxidant in nature. Protects against lipid peroxidation in membranes. Can donate a first e- and be stabilized by resonance, Second electron stabilized by oxidized Vit E.
Vitamin E deficiency
found in corn, nuts, olives, green vegetables, egg yolks. deficiency is uncommon. See hemolytic anemia, myopathy, and neurological defects
can donate 1e- to vitamin E for conversion back to reduced state. Important in collagen synthesis.
Ascorbic Acid deficiency
-citrus fruits, peppers, strawberries. Scurvey: impaired wound healing, bleeding eccymoses, swollen gums, anemia, lethargy, depression, corkscrew hairs.
Vitamin A, beta carotene. antioxidant .... quench singlet oxygen.
Vitamin A deficiency
number 1 cause of accidental blindness in the world, night blindness, follicular hyperkaratosis, xeropthalmia.
chelate Fe and prevent the fenton reaction. Donate electrons to superoxide or lipid peroxy radicles or complex them to stabilize them.
B cell Maturation
occurs in the marrow, does not require contact with antigen
expressed by pro and pre B cells. It adds random nucleotides for somatic mutations.
B cell staging
Stem cell, Pro, pre, Immature, mature, activated, memory B cell, Plasma cell.
present in stem and pro B cells, allowing attachment to their bone marrow receptor to allow for differentiation and growth.
Pre B cell
large and small (dividing status). As they become small pre-B cells, they begin to upregulate RAG1 and 2. They also express IL-7R and are stimulated to divide using IL7
Immature B cell
final stage of development in the marrow. Express IgM and later IgD. RAG1 and 2 downregulated. able to leave marrow and migrate.
Promotes B cell lineage development.
B- lymphocyte stimulator
Signals through BR3 for the survival of pre-immature B cell stages from transition stage onward.
are important in initiating B cell differentiation leading to division
Bruton's Tyrosine Kinase
Is a key enzyme involved in signal transduction downstream of the pre-BCR and BCR. defects lead to immunodeficiency XLA. patients have few circulating B cells and very low Ig. (agammaglobinemia).
T Independant antigen 1. Can activate B cells without MHC class II T-help. TI-1 are predominantly bacterial cell wall components, mostly LPS. Stimulate via TLR 4, only IgM is produced. produce poor memory.
predominantly large polysaccharide molecules with repeating antigenic determinants. ex. flagellin, ficoll. Can only stimulate B cells through the Bcell receptor. produce poor memory.
from Th1 leads to B cell division.
releases IL 4 5 6 10 13 for B cell differentiation.
Releases INF y for B cell differentiation.
T cell induction of B cells
produces better memory and involves cytokine release.
Antigen presenting cell
releases IL1 for B cell activation.
originate in the marrow, migrate to thymus T cell precursor DN1-4(double -), double positive cell (cd4 and cd8) then CD4 or CD8 positive and negative selection, migation to body
if a T cell comes across an APC, CD28 looks for B7 on the APC. if cannot find it it is anergy and T cell can no longer become activated, will die shorly.
Recognize proteins outside the TCR and couples TCR, CD28 and MHC not needing B7 for activation. Nonspecific activation and cytokine storm.
is Ckit. present in immature T cells D1 and 2 and less in D3 and low in D4
Present In Immature T cells D 1 and D2, absent in D3 and D4
Present in D2 and D3 absent in D1 and D4
Is the T cell receptor
Found on CD4 + T cells, after double positive stage
Found on CD8 + T cells, after double positive stage
Ckit (CD117)++, Cd44+, CD 25-
Ckit (CD117)++, Cd44+, CD 25+
Ckit (CD117)+, Cd44-, CD 25+
Ckit (CD117)low, Cd44-, CD 25-
MHC Class I
is the inhibatory signal for NK cells, activates CD8+ cells
Activated By MHC class1, costimulated by CD 28, B7 (from APC) interaction
naive T cells (precursor) CD8
Naive CTL P
does not express IL2 or IL2 P Expresses CD45RA, no cytotoxic activity.
High affinity for IL-2R, requires high levels of ILR to proliferate expresses CD45RO. Expresses high levels of the adhesion molecules CD2 and LFA-1. is cytotoxic
is part of CD8+ T cell receptor, increases and decreases its affinity to facillitate binding of the MHC class I.
perforinmolecules form a pore on target cell membranes. Granzyme molecules activate apoptosis by cleavage of caspases
binds to Fas on the membrane of target cells and initiates killing. activates apoptosis by cleavage of caspaces
is also secreted by CTLs leading to caspace impact and apoptosis.
do not need antigen to work, no mhc. produce INF y which tilts immune response toward TH1 cells and M1 macrophages. Kills via Fas, perforin and granzyme. TNF expression.
NK cell stimulation
Stimulated by IFNa, IFN B, IFN y, TNFa, and IL 15
NK cell receptors
have both activation and inhibition receptors
Lectin like receptors (NK)
Bind proteins rather than polysaccharides mostly activating
Immunoglobulin like receptors (NK)
killer cell immunoglobulin like receptors. Bind most MHC class I molecules. mostly inhibatory
broad MHC-I inhibatory
inhibatory signal(MHC I) trumps activating signal. kill with binding, perforins and granzymes
Little known about them. They express TCR, but different from CTLs. Mature in Thymus. Do not recognize MHC bound molecule.