D1 Immune Reponses

Question 1

why is co-stimulation required for activating Tc
Describe steps (3 important signals)

Answer 1

Naive Tc require more than 1 signal for activation & proliferation into effector Tc

Signal 1. antigen + MHC w/ TCR-CD3 complex
Signal 2. non-specific costimulatory signal CD28/B7 (CD80/CD86)
(may be inhibitory or stimulatory) (still energic)
Signal 3. additional co-stim signals: ICOS, OX40: influences Th polarization, cytokines, type of response & switch on/off: controls pathology

Question 2

what happens to mice lacking CD28/B7.1/B7.2

describe their expression

Answer 2

profoundly immunodeficient as lacking the most important co-stimulator
CD28 constitutively expressed on T cells (CD4/8)
B7.2 (CD86) expressed constitutively expressed at low levels and induced early after activation of APC
B7.2 = Th1
B7.1 (CD80) NOT expressed constitutively and induced hours.days after APC activation
B7.1 = Th2

Question 3

describe the role of CTLA-4

what happens to CTLA-4 deficient mice

Answer 3

checkpoint inhibitor
Binding of CTLA-4 & B7 on Tc inhibits activation
CTLA-4 KO have uncontrolled Tc proliferation = autoimmunity as Tc don’t become anergic following contact to antigen

Question 4

describe OX40 (CD134)

• where is it expressed?
• role?
• role in maintain immune system
• important in which Th responses

Answer 4

• Only on activated Tc and ligand on activated APC
• Binds to receptors on Tc preventing them from dying & subsequent increases cytokine production
• role in the maintenance of an immune response beyond the first few days and onwards to a memory response due to its ability to enhance survival
• Th1 & Th2

Question 5

describe ICOS

what production does this drive

Answer 5

• Inducible on effector cells after initial Tc activation
• -> Drives proliferation of effector Tc
• Important in germinal centre formation and T-dependant antibody responses
• More important in driving IL-4 and IL-10 production

Question 6

why is cytokine secretion brief & self-imitating. how is this brief action achieved.
What is synthesis controlled by

Answer 6

• to avoid cytokine-storm
• cytokines not usually stored (exception: TNFa in mast cells)
• controlled by new gene transcription

May be additionally controlled by RNA processing & Posttranscriptional processing e.g. proteolytic cleavage (IL-18, TNF-a - both are proproteins)

Question 7

which External signals regulate expression of cytokine receptors

Answer 7

Activation of T or Bc –> upregulated expression of receptors
may also be regulated by same or other cytokine
- Positive amplification
- Negative feedback

Question 8

Actions of cytokines (5)

Answer 8

Pleiotropy
Redundancy
Synergy
Antagonism
Cascade induction

Question 9

name the 5 major classes of cytokine receptors

Answer 9

1. Immunoglobulin superfamily receptors
2. Class I cytokine receptor family: haematopoietin receptor family
3. Class II cytokine receptors family: Interferon receptor family
4. TNF receptor family
5. Chemokine receptor family

Question 10

describe JAK/STAT

• signaling pathway for what type of receptors
• describe JAK
• describe STAT

Answer 10

Signaling pathway used by type I & II cytokine receptors
Janus kinase (JAK)
 - Protein kinase 
 - 2 sites
JAK will bind to different STATs 
STAT
 - Signal Transducer & Activator of Transcription
- Transcription factor