T cells

Question 1

Site of genereration of T cells

Answer 1

Thymus

Question 2

Functions of T cell subsets

Answer 2

CD8 (cytotoxic ) cells - Kill virus infected cells, tumour cells
CD4 (helper) cells - Produce cytokines, help B cells, macrophages

Question 3

Structure of T cell receptor

Answer 3

Alpha and beta chains
Variable and constant regions
Associated with signalling chains of CD3
T cell receptor recognises peptide on MHC
CD4 binds to MHC II
CD8 binds to MHC 1

Question 4

Site of location of immature T cells in Thymus

Answer 4

Cortex

Medulla has mature T cells

Question 5

Protein responsible for VDJ rearrangement in T cell receptor

Answer 5

RAG gene -RAG 1,2

Question 6

Role of IL-2

Answer 6

-IL-2 required for driving resting T cells
-Drives T reg cell induction
Acting via CD25
Induces Foxp3- master regulator of Treg cells

Calcineurin inhibiors -inhibit IL-2 induction

Question 7

Role of AIRE,FEZF2

Answer 7

Autoimmune regulator
Turns on expression of tissue specific Ags at low levels in thymus
Leads to deletion of high affinity T cells, induction of regulatory T cells

Question 8

Disease condition due to mutation of AIRE

Answer 8

Autoimmune Polyendocrine Syndrome 1
Chronic mucocutaneous candidiasis -due to ab against Th17
Autoimmune hypoparathyroidism
Autoimmune Addisons disease

Question 9

Signals in T cell activation

Answer 9

Signal 1-MHC and peptide

Signal 2 -Co-stimulation [mediated by B7.1(CD80),B7.2(CD86)]

Question 10

Role of CD28 on T cells

Answer 10

Leads to activation by interacting with costimulatory molecules

Question 11

Role of CTLA4

Answer 11

Induced slowly on T cells following activation
Stronger binding to B7 molecules
Generates negative signal-> turns off T cells

Question 12

Mechanisms of peripheral T cell tolerance

Answer 12

1. Inhibitory molecule engagement
2. Anergy
3. Clonal ignorance
4. Treg cells

Question 13

Inhibitory molecule engagement mechanism

Answer 13

CTLA4,PD-1 molecules expressed on T cells
Dysfunction lead to autoimmunity
PD1 blockade (check point inhibitor) ->immune S/E

Question 14

Clonal ignorance mechanism

Answer 14

Lymphocytes ignore low levels of self antigens- not enough to signal antigen receptor
If some exposure -secrete antiinflammatory cytokines-IL-10,TGF beta - turn into T reg cells

Question 15

Immune mechanism of villous atrophy in coeliac

Answer 15

HLA DQ2 or DQ8 restricted T cell immune reaction

Question 16

Marker of memory T cell

Answer 16

CD45 RO

Question 17

MHC class I expressed by all cells except

Answer 17

RBC

Question 18

Cytokine responsible for hyperalgesia

Answer 18

IL-1 beta

Question 19

T cell immunodeficiencies

Answer 19

Idiopathic CD4 lymphopenia
Chronic mucocutaneous candidiasis
Hyper IgE syndrome

Question 20

Markers of Treg cells

Answer 20

CD4 +
CD25 expression( IL-2R alpha)
foxp3 expression -master regulator of T cells

Question 21

MOA of superantigens

Answer 21

Bind outside MHC:peptide groove to Vbeta chain of T cell receptor
Does not require processing for MHC presentation
Stimulates 2-20% of T cells -> massive cytokine release-> TSS

Question 22

Subsets of helper T cells

Answer 22

Th1,Th2, Th 17

Question 23

Cytokines secreted by Th1 cells

Answer 23

INF-gamma, TNF, lymphotoxin

Question 24

Pathogenesis of MSMD(Mendelian Susceptibility to Mycobacterial Disease)

Answer 24

Deficiency of Th1 pathway
Th1 diffrentiate in response to IL-12,INF -gamma
Mainly involving intracellular pathogens
Non tuberculous mycobacteria,Invasive salmonellosis
TB,Severe viral infections

Question 25

Th2 cell deficiency causes which infections

Answer 25

``` Th-2 differentiate in response to IL-4 Secrete IL-4,5,6,10,13 Role in atopy , defence against helminths IL-4,IL-13 -> IgE production by B cells IL-5 -> Eosinophils ```

Question 26

Role of Th 17 cells

Answer 26

Differentiate in response to IL-1,IL-6,IL-23 Secrete IL-17, IL-22 IL-17-Acts on many cells- release chemokines,cytokines that attract neutrophils. Stimulates keratinocytes IL-22 -Stimulate release of defensins, other AMP Defense against Candida, staphylococcus Role in autoimmune disease

Question 27

Role of helper T cells

Answer 27

Express CXCR5, ICOS Secrete IL-21 Help B cells -class switching, affinity maturation

Question 28

Diagnosis of chronic mucocutaneous candidiasis

Answer 28

NBT test -negative in CGD

Question 29

IL secreted by Treg cells to suppress immune system

Answer 29

TGF beta, IL-10

Question 30

Disorders of Neutrophil phagocytic function

Answer 30

CGD Chediak Higashi Leukocyte adhesion deficiency Neutrophil enzyme deficiency -MPO, G6PD

Question 31

Interleukins produced by each T cells subset

Answer 31

Th1 -INF-gamma,lymphotoxin,TNF (intracellular pathog) Th2 -IL-4, IL-5,IL-6,IL-10,IL-13,TGF beta (helminths) Th17 -IL-17 (defence against candida and Staph)

Question 32

T cell imp in pathogenesis of sarcoidosis

Answer 32

Th1 helper T cell

Question 33

Mechanism by which HSV escapes APC

Answer 33

Production of Tap inhibitor protein-prevents transport of peptides to MHC Adeno virus- produces pn that anchors MHC in ER-> no surface expression of MHC CMV -accelerates transport of peptides out of ER- less chance of binding to MHC

Question 34

Main molecular defect in X linked SCID

Answer 34

Deficiency of cytokine receptor gamma common chain

Question 35

Defect in autosomal recessive SCID

Answer 35

JAK -3, IL-7 R alpha ,ZAP 70 defy, CD3 defy, RAG-1,2 deficiency

Question 36

Role of important classes of interleukins

Answer 36

IL 1- Macro, monocyte, DC -> inflammatory response, fever IL- 2 -Proliferation of Tcells IL- 3 -Hematopoietic lymphoid growth IL- 4 -Acts on B cells -Ig E switching IL- 5- Eosinophil growth and activation IL-6 -Differentiation of activated B cells to plasma cell IL- 8 -neutrophil chemotaxis IL-11 - stimulates megakaryocytes-> platelets

Question 37

IL-17 inhibitor in psoriasis

Answer 37

Secukinumab, Ixekizumab, Brodalumab

Question 38

IL-12/23 inhibitors

Answer 38

Ustekinumab

Question 39

TNF alpha inhibitors

Answer 39

Etanercept,adalimumab, Infliximab