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Flashcards in HDM Final Deck (148):
1

Ag recognition by TCRs. Leads. To the receptors doing what?

Clustering (this leads to an activating cascade)

2

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)

3

what cell marker is used to count total T cells ?

CD3

4

When the TCR is engaged to activate the T cell what co-stimulatory signal must be present

CD80-CD28

5

You require 100 fold fewer TCRs to cluster for activation when what is present?

Co-sitmulation (CD80-C28)

6

What state do T cells enter if they recognize antigen presentation without costimulation?

Anergy (functional inactivation)

7

What cytokine produced by newly activated T cells functions to stimulate T cell proliferation (autocrine signalling)

IL-2

8

What cytokine is also called T. Cell growth factor

IL-2

9

What surface receptor is present on activated T cells but not naiive T cells

IL-2 Receptor

10

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

11

What cytokines turn T cells into Th1

IFN gamma, TNF

12

What cytokines cause T cells to become Th2

IL4, 5, 10

13

What is T cell homing

Process of activated t cells going to tissue where the activating DC came from to fight the pathogen

14

Which cytokine is necessary for class switching to IgE

IL4

15

What cytokine is necessary to activate eosinophils

IL5

16

Th1. Cells produce which. Cytokines?

IFN gamma, IL2, TNF beta

17

Th2 Cells produce which. Cytokines?

IL4, 5, 10

18

This subset of Th cells activates macrophages, induces B cell production of opsonizing antibody

Th1

19

This subset of Th cells activates b cells to make neutralizing antibody (plus various effects on macrophages)

Th2

20

What controls the functional commitment of Th cells?

Tissue macrophages. And their products

21

Th1. Cells come to be when macrophages produce what cytokine????

IL12

22

Th2 Cells come to be when macrophages produce what cytokine????

IL4

23

What is the second costimulatory signal that is required for Th cells to activate macrophages and b cells?

CD40-CD40L

24

The binding of CD40-CD40L increases expression of what on the APC???

B7. And MHC

25

What are the main cells activated by Th1 cells?

INF-gamma activates macrophages and B cells (for Opsonization and phagocytosis)

26

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

27

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

28

CTL granules are exocytosed when they find a target cell. What is in these granules?

Perforin and granzyme

29

What process is induced by the enzyme "granzyme" in target cells?

Apoptosis

30

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

31

What are the two mechanisms of killing activated by CTLs?

Granzyme and perforin granules OR Fas-FasL binding

32

CTLs are unique because they express what surface ligand that can bind to target cell to initiate apoptosis

FasL

33

Do gamma-delta T cells express CD3? CD4? CD8?

3-yes
4 and 8- nope

34

Where do we find gamma-delta t cells?

Intestine, uterus, tongue

35

Without Th cells B cells can only. Produce Abs of what isotope?

IgM

36

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)

37

Gamma delta t cells can stimulate b cells to produce what isotype of antibody

IgE

38

By what mechanism can gamma delta t cells eliminate infected or stressed cells

Granzymes

39

What CD marker is analogous to Fas Receptor

CD95

40

Heterogenous group. Of t cells that recognize self and foreign lipids and glycolipids

NKT cell

41

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

42

Gamma delta T. Cells. Can present antigens via which MHC. Class?

II (just like. APCs)

43

Gamma delta T cells can trigger production of what cytokine? Which cell do. They cause to mature?

IL-12
DC

44

How do gamma delta t cells regulate stromal function

Produce growth factor

45

Normal t cells recognize ___ Ag's. NKT cells recognize ___ Ags.

Peptide, lipid or glycolipid

46

Tuberculosis is an example of one time that we utilize the killing done by which kind of immune cell?

NKT

47

NKT cells quickly produce large amounts of what cytokines?

INF-gamma, IL-4

48

what are materials that our immune cells recognize as "damaged"?

cytokines, pathogens, toxins, mechanical tissue damage, contents of dying cells

49

activated APCs express higher levels of what

both MHCII and B7

50

what kind of cell death generates danger signals which lead to inflammation

necrosis

51

what is the dirty form of cell death that causes swelling, rupture, inflammation or harm to neighboring cells?

necrosis

52

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

53

what are the stages of acute inflammation

1. Detect danger/ damage
2. Leukocyte recruitment/ eliminate stimuli
3. Resolution (macrophages clean up)
4. wound healing (angiogenesis, new epithelium and collagen)

54

what are the 3 signals released during cell necrosis that activate NF-kappa-B to begin causing inflammation

HMGB1, Uric acid, HSPs

55

what immune cell cleans debris using scavenger receptors (a PRR)

macrophage

56

macrophages release TFG beta which stimulus what cell make collagen

fibroblast

57

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

58

what cells contribute to the "cleanliness" of cell death via apoptosis

Treg (as well as IL-10 and TGF-beta)

59

when activated, caspases are the executioners of the cell during apoptosis. they act by destroying what key components of the cell?

cellular infrastructure

60

what are the apoptotic signals that trigger the intrinsic pathway

Bcl2, calcium, free radicals

61

what is the regulator of intrinsic apoptosis

cytochrome c

62

what are the executioners involved in intrinsic apoptosis

cas 9 then cas 3 (and apaf-1)

63

what triggers extrinsic apoptosis

Fas-FasL binding

64

what are the executioners of extrinsic apoptosis

cas 8, 10 then cas 3

65

what is the disorder that results from a defective Fas gene?

ALPS (autoimmune lymphoproliferative syndrome)

66

what are symptoms of ALPS

adenopathy, splenomegaly, over activation of B and T cells, lymphocytes live too long (malignancy)

67

before a b cell leaves the bone marrow it is tested for recognition of self Ags in a process called what

central tolerance

68

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)

69

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)

70

after a b cell is activated, it requires stimulation from what other immune cell before it can clonally expand

Th

71

What are 3 mechanisms for generating antibody or TCR diversity

Somatic recombination, junctional diversity, somatic hypermutation

72

Shuffling gene segments describes which of the 3 methods for inducing diversity in Ab and TCR?

Somatic recombination

73

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

74

One B cell can secrete one or more ___ of immunoglobulins but they will all respond to the same antigen

isotypes

75

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)

76

Kappa (light) chain of Ig is encoded on which chromosome?

2

77

lambda (light) chain of Ig is encoded on which chromosome?

22

78

The heavy chain of Ig. Is encoded on which chromosome

14

79

Which heavy chain domains contain 3 constant domains?

A and D and G

80

Which heavy chain domains contain 4 constant domains?

M and E

81

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)

82

Where would you find double positive T cells?

CD4+CD8+ deep in the thymic cortex

83

Where in the thymus do we find single positive T cells?

These mature T cells are found in the medulla

84

Expression of the Ig heavy chain requires what two Gene recombination events?

DJ joining followed by VDJ joining

85

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)

86

Which subunit of the TCR is analogous to an Ab light chain?

Alpha

87

The light and heavy chains are assembled where. In the cell?

ER

88

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

89

Which light. Chain has more diversity? (More genes to choose from in an undifferentiated cell?)

Kappa (300 compared to only 30 possibilities for lambda)

90

What portion of an Ab contains "complementarity determining regions"?

Light chains variable regions

91

The variable region of light chains contains one variable exon as well as what other exon?

Leader (L) exon

92

What enzyme is required for combinational diversity in antigen receptors?

VDJ recombinase (found in immature B and T cells- RAG genes)

93

What enzyme is required for junctional diversity in antigen receptors?

Exonuclease and TdT (this form of diversity is unliminted)

94

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)

95

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

96

Which Ab isotype is responsible for Mucosal immunity

IgA

97

Which Ab isotype is responsible for Which Ab isotype is responsible for naive BCR only

IgD

98

Which Ab isotype is responsible for mast cell activation and helminth defense

IgE

99

Which Ab isotype is responsible for opsonization, complement activation, ADCC, and neonatal immunity

IgG

100

Which Ab isotype is responsible for naive BCR and complement activation

IgM

101

Isotype switching occurs by deletion of DNA segments assisted by what enzyme?

AID

102

Isotype switching occurs only after a B cell is stimulated by what?

CD40-CD40L

103

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)

104

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)

105

MHC is a large gene on which human chromosome

6 (on the P arm)

106

Which class of MHC. Molecules has more diversity?

Class II can express 10-20 different molecules (Class I can express a measly 6)

107

HLA class III codes for what in human cells?

Complement proteins (C4, Factor B, C2) and cytokines (LTb, TNFa, LTa)

108

Graft between two areas on the same individual

Autograft

109

Graft (transplant) between 2 genetically identical individuals

Isograft

110

Graft between genetically different members of the same species

Allograft

111

Graft between members of different species

Xenograft

112

What elements must be tested before tissue transplantation can occur

ABO typing, HLA typing, screen preformed Abs, crossmatching

113

When the respiratory tract and lungs become involved in an allergic reaction the mediators cause what to happen

Anaphylaxis

114

Activated B cells proliferate, secrete IgM, and increase expression of what

MHC II with Ag, B7, and cytokine receptors

115

Which B cell receptor binds complement protein C3d that has opsonized bacteria

CR2

116

Once a B cell is activated in the lymphoid follicle where does it migrate to?

Toward t cell rich zones of LN

117

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)

118

Deficiency in CD40L (X linked disorder) Signaling during B cell activation leads to what?

Hyper IgM syndrome (CD40 required for class switching)

119

What two fates does an active b cell have?

Plasma cell or memory cell

120

These cells travel to spleen or bone marrow to produce lots of antibodies

Plasma cells (only alive 5 days)

121

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

122

What are examples of TI antigens

Polysaccharides, lipids, and other nonprotein Ags

123

How do TI Ags activate B cells to induce an adaptive immune response?

Cross linking of the BCRs

124

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

125

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)

126

What is the most important application of our body's use of TI Ag defense

Ab against encapsulated bacteria (and its fast)

127

What causes tissue injury during an infection?

Host response (collateral damage) and bacterial toxins

128

What does C reactive protein do (CRP)?

Its an acute phase protein: Binds bacterial Polysaccarides, activate complement

129

What cytokine increases the presence of CRP?

IL-6

130

DCs recognize bacteria using what?How to they migrate through the body to. Activate. Naive T cells??

PRRs (Like TLRs)

Migrate via lymphatics

131

Local inflammation causes lymph nodes to increase adhesion molecules on their ___ so that DCs are able to enter the LN

High endothelial venule

132

Which kind of bacterial toxin are components of the cell wall

Endotoxin (LPS)

133

Which type of bacterial toxin are secreted by the bacteria

Exotoxin

134

This bacterial exotoxin shuts down protein synthesis

Diptheria toxin

135

This bacterial exotoxin interferes with ion/water transport

Cholera toxin

136

This bacterial exotoxin inhibits neuromuscular transmission

Tetanus toxin

137

Peptidoglycan and LPS activate complement via which pathway?

Alternative

138

complement activation results in what outcome for the bacteria

Opsonization, phagocytosis, or lysis

139

Which complement pathway requires C1r, C1s, and C1q in step 1?

Classical

140

Which complement pathway requires MBL and MASPs in step 1?

mannose binding lectin

141

Which complement pathway requires Factor B and Factor D in step 1?

Alternative

142

What is needed in the alternative pathway to stabilize the convertase that is made (such as c3 convertase= C3bBb)

Properdin

143

Which ROS has the ability to initiate apoptosis (via caspase activation) or necrosis?

Peroxynitrite (ONOO-)

144

While many bacteria can inhibit complement activation, which is known for resisting phagocytosis?

Pneumococcus, neisseria meningitis

145

While many bacteria can inhibit complement activation, which is known for scavenging ROS?

Catalase positive staph

146

Which antibody and antibody receptor are required to undergo Ab. Mediated phagocytosis

IgG binds Fc-gamma-RI

Or

IgA binds F-alpha-RI

147

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)

148

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)