Exam Questions

Question 1

What is tolerance?

Answer 1

• many layers of protection imposed by immune system to prevent reaction of its cells/ antibodies against host components

Question 2

What are the 3 mechanisms of tolerance?

Answer 2

• Evasion- how location/ sequestration has a role in protecting some sites/ tissue-specific antigens found there from exposure to immune system (passive process)
• Elimination- mechanisms that remove self-reactive lymphocytes before they can do damage (negative selection)
• Engagement- cultivating certain self-reactive cells for protection of self structures (regulatory phenotype)

Question 3

How do regulatory CD4+ T cells (tTregs/ pTregs) inhibit immune responses?

> FoxP3/ CTLA-4/ IL-2R α chain (CD25)

Answer 3

• Contact-Dependent Mechanisms- interaction of CTLA-4 (Tregs) and CD80/86 (APCs) inhibits APC function
  > decreased expression of CD80/86
  > activation of IDO > creating an immunoinhibitory microenvironment
• Contact-Independent Mechanisms
  > secretion of immune-inhibitory cytokines (IL-10/ TGF-β/ IL-35) into surrounding area > shuts down nearby T cells/ APCs
  > due to high CD25 (IL-2Rα) expression, Tregs absorb IL-2 > prevents expansion of effector T cells

Question 4

What is linked suppression? > mediated by Tregs

Answer 4

• Tregs can inhibit both effector T cells that share the same antigen specificity/ T cells that recognize other antigens
  > occurs when both Treg/ T-cell recognizing another antigen interact with same APC
• when a single APC simultaneously interacts with T cells of different specificity > inhibitory signals meant for one can be transmitted to both > leads to spreading of immune suppression to include other antigens

Question 5

What happens in Hashimoto’s thyroiditis?

Answer 5

• autoantibodies/ TH1 cells specific for thyroid antigens are produced
• DTH response > thyroid gland infiltration by lymphocytes/ macrophage/ plasma cells
• inflammatory response caused by antibodies against thyroid proteins

Question 6

What happens in type 1 diabetes (IDDM)?

Answer 6

• autoimmune attack against insulin-producing beta cells in pancreas
• starts with CTL infiltration/ macrophage activation (insulitis) > cell-mediated DTH response > autoantibodies/ cytokine release
• beta-cell destruction mediated by auto-antibodies (ADCC/ antibody-mediated complement lysis)/ cytokines/ lytic enzymes released from activated macrophages

Question 7

What happens in myasthenia gravis?

Answer 7

• autoimmune disease mediated by blocking antibodies
• auto-antibodies bind to AChR on muscles > block ACh binding > induce complement-mediated lysis of cells
• type II hypersensitivity

Question 8

What happens in lupus?

Answer 8

• auto-antibodies to cells/ cellular components (DNA/ histones/ clotting factors/ RBCs/ leukocytes)
• immune complexes of auto-antibodies/ antigens deposit along blood vessel walls > type III hypersensitivity
• complement system activation > MAC/ C3a/ C5a

Question 9

What happens in multiple sclerosis?

Answer 9

• production of autoreactive CD4+ T cells
• TH17 cells > IL-17 is hallmark

Question 10

What happens in rheumatoid arthritis?

Answer 10

• production of antibodies that react with citrullinated protein antigens
• production of auto-antibodies (RFs) > specific for Fc region of IgG
• immune complexes formed by RFs binding to normal circulating IgG are deposited into joints
• activates complement system > type III hypersensitivity

Question 11

What are 2 systemic autoimmune conditions caused by disruptions in immune regulation?

Answer 11

• APS-1- mutations in AIRE gene > critical for central tolerance in thymus (ensures tissue-specific antigens expressed during T cell development) > both elimination/ engagement
• IPEX- mutations in FoxP3 gene > master TF associated with regulatory T cells (both tTregs/ pTregs > central/ peripheral tolerance)

Question 12

What are the 3 categories of current therapies to treat autoimmune disease?

Answer 12

• broad-spectrum immunosuppressive treatments > anti-inflammatory
• immunosuppression directed at specific cells/ pathways
• targeted immunotherapy > guide hots cells to new pathway

Question 13

What are the 5 main mechanisms of action of treatments for autoimmune disease?

Answer 13

• T/ B cell-depleting agents
• targeting cell trafficking/ adhesion > fingolimod
• targeting TCR signaling
• targeting costimulatory/ accessory molecules > CTLA-4
• targeting cytokines/ cytokine signaling

Question 14

How are mucosal/ barrier responses typically controlled?

Answer 14

• TH2 response:
  > activation of ILC-2s
  > TH2 specific cytokines > IL-4/ IL-5/ IL-13
  > IgE > recognizes cell surface epitopes of pathogen
  > dimeric IgA at mucosal surfaces

Question 15

What are the immune mediators for extracellular infections?

Answer 15

• PRRs on phagocytic cells
• complement system activation
• antimicrobial compounds
• IgG/ IgM/ mIgA antibodies
• TFH/ TH17/ TH2 cells

Question 16

What are the immune mediators for pathogens in intracellular vesicles?

Answer 16

• TH1 DTH response
• TH1 cytokine IFN-γ > activates macrophages to digest vesicle-bound agents

Question 17

What are the immune mediators for pathogens within the cytosol? (all viruses)

Answer 17

• detected by cytosolic PRRs (NLRs/ RLRs) > cytokine secretion/ inflammasome activation/ induction of cytotoxic cells to kill infected host cells: NK cells/ CTLs
• NK cells detect cell surface changes associated with infection/ kill infected host cells via ADCC
• CTLs activated by cross-presentation of antigen by TH1-licensed DCs > primary adaptive mediators of infected target cell killing

Question 18

What are the mechanisms of antigen delivery from the intestinal lumen to APCs?

Answer 18

• M cells > transcytose antigen/ some microbes from lumen
• FcRs > carry antigen-antibody complexes across epithelial cells
• Goblet cells > transcytose small antigens
• Direct APC contact > APCs can extend their processes into lumen

Question 19

What are the innate immune effector mechanisms that eliminate many viral infections?

Answer 19

• complement activation
• antimicrobial peptides
• recognition of viral PAMPs (dsRNA) by PRRs > induces type I IFN expression (IFN-α/ IFN-β)/ inflammasome assembly/ activation of NK cells

Question 20

What is the IFN antiviral pathway?

Answer 20

• IFN-α/ IFN-β bind to/ dimerize IFNAR
• this recruits/ activates JAK1/ TYK2 > bind/ phosphorylate STAT1/ STAT2 > dimerize/ enter nucleus > stimulate expression of antiviral genes

Question 21

What are the 4 IFN-stimulated antiviral genes?

Answer 21

• PKR- inhibits elf2α > inhibits translation
• 2’,5’-oligo-A-synthetase > degrades viral/ cellular mRNA
• Mx proteins- self assemble into ring-like structures > inhibit viral replication
• IFIT proteins- bind to viral RNA > inhibit translation

Question 22

What are the cell-mediated mechanisms for viral infections?
> required once viral genome integrated into host chromosomal DNA

Answer 22

• CD8+ Tc cells/ CD4+ TH1 cells
• activated TH1 cells produce IFN-γ (antiviral)/ IL-2 (activates effector T cells)/ TNF-α
• TH1 cells license DCs for cross-presentation

Question 23

What is required for activation of naive Tc cells by exogenous antigen?

Answer 23

• DC licensing by TH cell
  > DCs internalize/ process antigen via exogenous pathway > present to CD4+ TH cells via MHC II
• DC cross-presentation > activation of CTLs
  > Th cells are bridge > license DCs to cross-present internalized antigen via MHC I > provide local IL-2 to help activate CTL

Question 24

What 4 strategies do viruses employ to evade host defence mechanisms?

Answer 24

• evade action of IFN-α/ IFN-β
• inhibit antigen presentation by infected host cells
• change surface antigens
• cause immunosuppression

Question 25

What is original antigenic sin?

Answer 25

- Fc regions of antibodies bound to surface of pathogen bind to FcRs on naive B cells > inhibit them from responding to new epitopes - no immune response mounted to each new epitope during subsequent pathogen exposures > until pathogen expresses a significant # of unique epitopes/ memory cells can no longer eradicate pathogen - primary response > activation of naive B cells - secondary response > reactivation of memory B cells

Question 26

What 4 strategies does plasmodium (protozoan parasite) have to evade immune system? > malaria

Answer 26

- changing its surface molecules > continual change in antigens seen by immune system - intracellular phases of life cycle > reduce degree of immune activation by pathogen - short time circulation in blood > most accessible stage - sloughing off its surface antigens > antibodies ineffective