HDM Final Flashcards
Ag recognition by TCRs. Leads. To the receptors doing what?
Clustering (this leads to an activating cascade)
Signalling is mediated by what membrane bound proteins in the TCR?
CD3 and zeta chains (because they have the long cytoplasmic tails with the ITAMS or ITIMS)
what cell marker is used to count total T cells ?
CD3
When the TCR is engaged to activate the T cell what co-stimulatory signal must be present
CD80-CD28
You require 100 fold fewer TCRs to cluster for activation when what is present?
Co-sitmulation (CD80-C28)
What state do T cells enter if they recognize antigen presentation without costimulation?
Anergy (functional inactivation)
What cytokine produced by newly activated T cells functions to stimulate T cell proliferation (autocrine signalling)
IL-2
What cytokine is also called T. Cell growth factor
IL-2
What surface receptor is present on activated T cells but not naiive T cells
IL-2 Receptor
When T cells are restimulated for a second time by an APC they begin to secrete cytokines which commit the T cell to what ?
Th1 or Th2
What cytokines turn T cells into Th1
IFN gamma, TNF
What cytokines cause T cells to become Th2
IL4, 5, 10
What is T cell homing
Process of activated t cells going to tissue where the activating DC came from to fight the pathogen
Which cytokine is necessary for class switching to IgE
IL4
What cytokine is necessary to activate eosinophils
IL5
Th1. Cells produce which. Cytokines?
IFN gamma, IL2, TNF beta
Th2 Cells produce which. Cytokines?
IL4, 5, 10
This subset of Th cells activates macrophages, induces B cell production of opsonizing antibody
Th1
This subset of Th cells activates b cells to make neutralizing antibody (plus various effects on macrophages)
Th2
What controls the functional commitment of Th cells?
Tissue macrophages. And their products
Th1. Cells come to be when macrophages produce what cytokine????
IL12
Th2 Cells come to be when macrophages produce what cytokine????
IL4
What is the second costimulatory signal that is required for Th cells to activate macrophages and b cells?
CD40-CD40L
The binding of CD40-CD40L increases expression of what on the APC???
B7. And MHC
What are the main cells activated by Th1 cells?
INF-gamma activates macrophages and B cells (for Opsonization and phagocytosis)
What are the main cells activated by Th2 cells?
IL4 causes B cell to class switch to IgE which activates Mast cells IL5 activates eosinophils
Although not necessary for activation of CD8 T cells, the binding of what will enhance APC’s ability. To stimulate the. CTL???
Th1 cells bind to APC using CD40-CD40L
CTL granules are exocytosed when they find a target cell. What is in these granules?
Perforin and granzyme
What process is induced by the enzyme “granzyme” in target cells?
Apoptosis
What is the function of granzyme and. Perforin in CTL killing of target cells?
They enter the target cell by endocytosis
perforin- pokes holes in the vesicle membrane
Granzyme- enter cytoplasm through those holes and activate apoptotic pathway
What are the two mechanisms of killing activated by CTLs?
Granzyme and perforin granules OR Fas-FasL binding
CTLs are unique because they express what surface ligand that can bind to target cell to initiate apoptosis
FasL
Do gamma-delta T cells express CD3? CD4? CD8?
3-yes
4 and 8- nope
Where do we find gamma-delta t cells?
Intestine, uterus, tongue
Without Th cells B cells can only. Produce Abs of what isotope?
IgM
Gamma delta t cells kill cells that become stressed by microbial infection without which restriction required by traditional alpha beta t cells
not MHC restricted (don’t need APCs to recognize Ag)
Gamma delta t cells can stimulate b cells to produce what isotype of antibody
IgE
By what mechanism can gamma delta t cells eliminate infected or stressed cells
Granzymes
What CD marker is analogous to Fas Receptor
CD95
Heterogenous group. Of t cells that recognize self and foreign lipids and glycolipids
NKT cell
What MHC Like molecule is recognized by NKT cells and what kind of antigen do they contain?
CD1d (acts like MHC)
lipids and glycolipids Ags
Gamma delta T. Cells. Can present antigens via which MHC. Class?
II (just like. APCs)
Gamma delta T cells can trigger production of what cytokine? Which cell do. They cause to mature?
IL-12
DC
How do gamma delta t cells regulate stromal function
Produce growth factor
Normal t cells recognize ___ Ag’s. NKT cells recognize ___ Ags.
Peptide, lipid or glycolipid
Tuberculosis is an example of one time that we utilize the killing done by which kind of immune cell?
NKT
NKT cells quickly produce large amounts of what cytokines?
INF-gamma, IL-4
what are materials that our immune cells recognize as “damaged”?
cytokines, pathogens, toxins, mechanical tissue damage, contents of dying cells
activated APCs express higher levels of what
both MHCII and B7
what kind of cell death generates danger signals which lead to inflammation
necrosis
what is the dirty form of cell death that causes swelling, rupture, inflammation or harm to neighboring cells?
necrosis
chronic inflammation causes a lot more long term damage to the body. what is the cellular response primary consisting of for acute inflammation? chronic inflammation?
acute- neutrophils
chronic- monocytes, macrophages, lymphocytes
what are the stages of acute inflammation
- Detect danger/ damage
- Leukocyte recruitment/ eliminate stimuli
- Resolution (macrophages clean up)
- wound healing (angiogenesis, new epithelium and collagen)
what are the 3 signals released during cell necrosis that activate NF-kappa-B to begin causing inflammation
HMGB1, Uric acid, HSPs
what immune cell cleans debris using scavenger receptors (a PRR)
macrophage
macrophages release TFG beta which stimulus what cell make collagen
fibroblast
in atherosclerosis, a macrophage enters the tissue and is activated via TLRs where it causes an inflammation. when macrophages in these circumstances accumulate lipids what kind of cell do they become?
foam cells
what cells contribute to the “cleanliness” of cell death via apoptosis
Treg (as well as IL-10 and TGF-beta)
when activated, caspases are the executioners of the cell during apoptosis. they act by destroying what key components of the cell?
cellular infrastructure
what are the apoptotic signals that trigger the intrinsic pathway
Bcl2, calcium, free radicals
what is the regulator of intrinsic apoptosis
cytochrome c
what are the executioners involved in intrinsic apoptosis
cas 9 then cas 3 (and apaf-1)
what triggers extrinsic apoptosis
Fas-FasL binding
what are the executioners of extrinsic apoptosis
cas 8, 10 then cas 3
what is the disorder that results from a defective Fas gene?
ALPS (autoimmune lymphoproliferative syndrome)
what are symptoms of ALPS
adenopathy, splenomegaly, over activation of B and T cells, lymphocytes live too long (malignancy)
before a b cell leaves the bone marrow it is tested for recognition of self Ags in a process called what
central tolerance
b cells are cooler than t cells because if one is made and found to have strong recognition of self, t cells just get killed but b cells can do what?
receptor editing (they get a second try to express a different antigen receptor that won’t be self reactive)
which chain of the BCR undergoes “receptor editing” after it is determined that recognition of self Ag is too strong?
light chain (first try is kappa, second try is lambda)
after a b cell is activated, it requires stimulation from what other immune cell before it can clonally expand
Th
What are 3 mechanisms for generating antibody or TCR diversity
Somatic recombination, junctional diversity, somatic hypermutation
Shuffling gene segments describes which of the 3 methods for inducing diversity in Ab and TCR?
Somatic recombination
Every B cell (and every plasma cell or antibody created from that B cell) undergoes genetic rearrangement so that it can recognize how many kinds of foreign antigens?
ONE
One B cell can secrete one or more ___ of immunoglobulins but they will all respond to the same antigen
isotypes
An Ig contains 2 identical light chains that are in one of 2 conformations. What are the 2 possible light chain conformations? And what process allows us to switch to the other conformation?
Kappa and lambda
Receptor editing (allows us to switch from kappa to lambda if kappa just aint doin the trick)
Kappa (light) chain of Ig is encoded on which chromosome?
2
lambda (light) chain of Ig is encoded on which chromosome?
22
The heavy chain of Ig. Is encoded on which chromosome
14
Which heavy chain domains contain 3 constant domains?
A and D and G
Which heavy chain domains contain 4 constant domains?
M and E
Where would you find double negative T cells
CD4-CD8-
These precursors are made in the bone marrow and travel to the thymus (seen specifically in the SUBCAPSULAR CORTEX of the thymus)
Where would you find double positive T cells?
CD4+CD8+ deep in the thymic cortex
Where in the thymus do we find single positive T cells?
These mature T cells are found in the medulla
Expression of the Ig heavy chain requires what two Gene recombination events?
DJ joining followed by VDJ joining
After recombination of the VDJ regions of the heavy chain occurs what sequence of events follows to complete somatic recombination
Introns are deleted, transcription, VDJ is spliced, mRNA is translated to produce heavy chain (light chain follows afterward with the same sequence but without a D segment)
Which subunit of the TCR is analogous to an Ab light chain?
Alpha
The light and heavy chains are assembled where. In the cell?
ER
In the human kappa (light chain) gene how many segments are there for the V region? J region? C region?
Kappa
V: up to 35
J: 5
C: 1
Which light. Chain has more diversity? (More genes to choose from in an undifferentiated cell?)
Kappa (300 compared to only 30 possibilities for lambda)
What portion of an Ab contains “complementarity determining regions”?
Light chains variable regions
The variable region of light chains contains one variable exon as well as what other exon?
Leader (L) exon
What enzyme is required for combinational diversity in antigen receptors?
VDJ recombinase (found in immature B and T cells- RAG genes)
What enzyme is required for junctional diversity in antigen receptors?
Exonuclease and TdT (this form of diversity is unliminted)
What enzyme takes nucleotides that aren’t originally in germline and adds them ranomly to sites of VDJ recombination to create Ig or TCR variation
terminal deoxyribonucleotidyl transferase (TdT)
One of the most variable CDRs is CDR3 (very important site for antigen recognition) and the junction that encodes this is located where
Within V region
Which Ab isotype is responsible for Mucosal immunity
IgA
Which Ab isotype is responsible for Which Ab isotype is responsible for naive BCR only
IgD
Which Ab isotype is responsible for mast cell activation and helminth defense
IgE
Which Ab isotype is responsible for opsonization, complement activation, ADCC, and neonatal immunity
IgG
Which Ab isotype is responsible for naive BCR and complement activation
IgM
Isotype switching occurs by deletion of DNA segments assisted by what enzyme?
AID
Isotype switching occurs only after a B cell is stimulated by what?
CD40-CD40L
After a BCR. Has been exposed to. An epitope and memory B cells are restimulated there is rapid proliferation in the germinal center of lymph follicles followed by selection of high affinity B cells that accumulate point mutations which do what?
Affinity maturation (make the B cell more capable of binding its antigen)
This process occurs when cytosine bases are deaminated and converted to uracil which get replaced by error prone DNA repair leading to mutations
Somatic hypermutation (affinity maturation)
MHC is a large gene on which human chromosome
6 (on the P arm)
Which class of MHC. Molecules has more diversity?
Class II can express 10-20 different molecules (Class I can express a measly 6)
HLA class III codes for what in human cells?
Complement proteins (C4, Factor B, C2) and cytokines (LTb, TNFa, LTa)
Graft between two areas on the same individual
Autograft
Graft (transplant) between 2 genetically identical individuals
Isograft
Graft between genetically different members of the same species
Allograft
Graft between members of different species
Xenograft
What elements must be tested before tissue transplantation can occur
ABO typing, HLA typing, screen preformed Abs, crossmatching
When the respiratory tract and lungs become involved in an allergic reaction the mediators cause what to happen
Anaphylaxis
Activated B cells proliferate, secrete IgM, and increase expression of what
MHC II with Ag, B7, and cytokine receptors
Which B cell receptor binds complement protein C3d that has opsonized bacteria
CR2
Once a B cell is activated in the lymphoid follicle where does it migrate to?
Toward t cell rich zones of LN
Active Th cells are Necessary To activate Memory B cells. What Costimulatory molecule is used in this interaction?
CD40 (B cell) binds CD40L (T cell)
Deficiency in CD40L (X linked disorder) Signaling during B cell activation leads to what?
Hyper IgM syndrome (CD40 required for class switching)
What two fates does an active b cell have?
Plasma cell or memory cell
These cells travel to spleen or bone marrow to produce lots of antibodies
Plasma cells (only alive 5 days)
State whether the following are characteristic of thymus dependent or thymus independent reactions: isotype switching, affinity maturation, memory B cell formation
All are thymus dependent (TD) because they require T cells
What are examples of TI antigens
Polysaccharides, lipids, and other nonprotein Ags
How do TI Ags activate B cells to induce an adaptive immune response?
Cross linking of the BCRs
There are two types of TI Ags: which type Are polyclonal activators of b cells? (First signal is Ag binding BCR, second signal comes from TLR)
TI-1
There are two types of TI Ags: which type are Ag with repeating epitopes for cross linking BCRs? (First signal is Ag binds BCR, then BCRs cluster to activate)
TI-2 (no memory)
What is the most important application of our body’s use of TI Ag defense
Ab against encapsulated bacteria (and its fast)
What causes tissue injury during an infection?
Host response (collateral damage) and bacterial toxins
What does C reactive protein do (CRP)?
Its an acute phase protein: Binds bacterial Polysaccarides, activate complement
What cytokine increases the presence of CRP?
IL-6
DCs recognize bacteria using what?How to they migrate through the body to. Activate. Naive T cells??
PRRs (Like TLRs)
Migrate via lymphatics
Local inflammation causes lymph nodes to increase adhesion molecules on their ___ so that DCs are able to enter the LN
High endothelial venule
Which kind of bacterial toxin are components of the cell wall
Endotoxin (LPS)
Which type of bacterial toxin are secreted by the bacteria
Exotoxin
This bacterial exotoxin shuts down protein synthesis
Diptheria toxin
This bacterial exotoxin interferes with ion/water transport
Cholera toxin
This bacterial exotoxin inhibits neuromuscular transmission
Tetanus toxin
Peptidoglycan and LPS activate complement via which pathway?
Alternative
complement activation results in what outcome for the bacteria
Opsonization, phagocytosis, or lysis
Which complement pathway requires C1r, C1s, and C1q in step 1?
Classical
Which complement pathway requires MBL and MASPs in step 1?
mannose binding lectin
Which complement pathway requires Factor B and Factor D in step 1?
Alternative
What is needed in the alternative pathway to stabilize the convertase that is made (such as c3 convertase= C3bBb)
Properdin
Which ROS has the ability to initiate apoptosis (via caspase activation) or necrosis?
Peroxynitrite (ONOO-)
While many bacteria can inhibit complement activation, which is known for resisting phagocytosis?
Pneumococcus, neisseria meningitis
While many bacteria can inhibit complement activation, which is known for scavenging ROS?
Catalase positive staph
Which antibody and antibody receptor are required to undergo Ab. Mediated phagocytosis
IgG binds Fc-gamma-RI
Or
IgA binds F-alpha-RI
Fc-epsilon-RI is special because it can bind IgE without an Ag bound (priming the cells). Which cells have Fc-epsilon-RI ?
Mast cell, eosinophil, basophil (binding of Ag causes granule exocytosis)
What are some methods used by bacteria to evade our immune system?
Antigenic variation
inhibit complement (block C3 convertase or MAC formation)
resist phagocytosis
scavenge ROS (catalase + bacteria)
