Immunopathology Type 4 (complete)

Question 1

Define Type IV immunopathology

Answer 1

• T cell mediated immune response
• Don’t require Ab or B cells but may involve them at some point in a disease

Can be helpful or hurtful!

Question 2

Describe TB testing on a cellular/molecular level, specifically the events following intradermal injection of TB Ag

Answer 2

Mantoux skin test

• Ag taken up by local macros/DCs and presented on MHC Class II
• If the person has any Th1 memory cells, they will see the APC, get stimulated, produce IFN-gamma and attract macros!

Represents a cellular infiltrate! One Th1 attracts 1000 macros

Question 3

Which cells would be seen in a 48-hr biopsy of the site where the TB Ag is administered?

Answer 3

Macrophages!!!

B/c if Th1 memory cells are stimulated, IFN-gamma is released, and attracts a shit ton of macros to the site

Question 4

What are the two phases of delayed hypersensitivity?

Answer 4

1) Initiation phase (immunization phase)

2) Elicitation phase (effector phase)

Question 5

Describe the initiation phase of delayed hypersensitivity

Answer 5

When a compound binds to/presented on MHC of DCs —» travels to lymph nodes —» presents to Th0 —» begins division into Th1 and Th17

These increase in numbers, but in the case of poison ivy the compound is washed/worn off before a rxn —» you’ve become immunized (created memory T cells)

Question 6

Describe the elicitation phase of delayed hypersensitivity

Answer 6

• Exposure to a compound like poison ivy —> memory T cells are activated —» secrete IFN-gamma, attracts macros —» inflammation visible at 6-12 hrs, peaks at 24-48 hrs
• Bypasses Th0 differentiation phase

IMPORTANT: memory T cells have a lower activation threshold (less Ag can elicit a rxn)

Question 7

Explain why a person has no observed symptoms when first exposed to poison ivy

Answer 7

Think: initiation phase of delayed hypersensitivity

Compound usually washed/worn off by the time Th1/Th17 are produced —» no activation of these cells, only memory T cells produced

Question 8

Describe how a chemical/small peptide might NOT need to be processed through an APC to be presented by that cell to T cells

Answer 8

They can just bind directly on the outside —> doesn’t need to be eaten, broken down, and presented

Question 9

Why do those who have received the BCG vx test positive for the PPD?

Answer 9

B/c the bovine TB (used in the vx) is CROSS-REACTIVE with human TB

Then they have to get the chest xray to prove they don’t have it (or do a QuantiFERON gold test)

Question 10

Describe the Quantiferon TB Gold test

Answer 10

• Preferred over skin testing
• Purified human TV proteins are added to whole blood sample —» incubated
• Th1 will recognize the Ag —> release IFN-gamma
• IFN-gamma is measured in a ELISA assay

Epitopes specific to humans, no cross-reactivity —» negative in those who had BCG

Question 11

Describe the problem that HLA-B*5701 people may have with the HIV drug abacavir

Answer 11

Abacavir hypersensitivity syndrome

• Difficult to diagnose correctly
• HLA-B*5701 is Class I , not II (which is recognized by Th1)
• Abacavir changes the structure of HLA-B*5701 —» binds certain self-peptides that aren’t normally presented
• pts are tested for this before given abacavir

LEADS TO: a drug-induced autoimmune rxn

Question 12

Discuss in principle how T cell immunity could be measured in a laboratory

Answer 12

Whole blood/WBCs can be incubated with Ag in a culture

Observed for:

1) Increased proliferation
2) Increased cell size
3) Cytokine production
4) DNA synthesis

Question 13

Why can TB skin tests be administered repeatedly to the same subject?

Answer 13

TB tests are not immunizing —» they can be repeated regularly w/o the subject becoming positive

Dose in PPD is too low to begin the initiation phase of delayed hypersensitivity

Question 14

Describe first-set graft reaction

Answer 14

• Graft from mouse A to mouse M —»> rejected in 10-20 days
• Recipient has 5-10% of T cells that can react w/ foreign MHC b/c some foreign MHCs look like self-MHC + peptide
• mouse M develops more anti-A Th1 and CTL

THINK: initiation phase of grafts :D

Question 15

Describe second-set graft reaction

Answer 15

• Another graft from mouse A to mouse M —» rejected in 5-10 days
• A result from memory T cells developed during first-exposure

THINK: elicitation phase of grafts!!

Question 16

Define hyperacute rejection.

Answer 16

AKA: white graft rxns

• When you keep putting foreign grafts on mouse M —» body will reject it before it heals (white and bloodless)
• B/c of Abs to histocompatibility Ags

Question 17

How can autoimmunity result from environmental exposure to tissues that cross-react with human organs?

Answer 17

For example: when brain is inhaled

• Normally: Brain is antigenic, not immunogenic —» so not a problem as long as it’s separated
• If brain is picked up by DCs (maybe b/c it’s inhaled) then it becomes an immunogen —» activates T cells —» attack corresponding organ (then they go all the way to the brain)

Question 18

Describe how MS relates to T cell reactivity and the Aire gene

Answer 18

• Myelin based protein is not upregulated by Aire during T cell development in the thymus
• Developing T cells are not exposed to MBP —» in MS, T cells are reactive to the autoAg (MBP)

Tx: T cell depletion – also B cell depletion b/c then T cells can’t be activated (fewer APCs)

Question 19

What are the 3 requirements for GvHD to occur?

Answer 19

1) Graft must contain immunocompetent T cells (even BM has mature T cells in it)
2) Must be >1 Ag in host which graft’s T cells recognize — Twins? no worries here
3) Host must be relatively immunoincompetent/unable to recognize graft’s MHC Ags —» otherwise graft would be rejected too rapidly

Question 20

Define the GvL phenomenon

Answer 20

• No GvH, ^ likelihood of leukemia relapse (those who receive T-cell depleted BM or pre-treatment BM from themselves)
• A little GvH symptoms are necessary to keep the leukemia from relapsing (need some mature T cells in the BM transplant)
• GvL rxn is considered an important part of a successful BM transplant

Question 21

Describe how molecular mimicry of a virus plays a roll in MBP breakdown

Answer 21

• Exposure to a virus in the brain stimulates T cells to attack and kill it
• You’ll feel better at first –» then bad again b/c T cells stick around attack the brain now that they are on the other side of the BBB

LEADS TO: Encephalitis

Question 22

Describe the role of Th2 cells in immunopathology

Answer 22

• Th2 cells found in periphery of certain inflammatory/infectious states (e.g. asthma, chronic worm infestation)
• Activate macros —» produce fibrosis in chronic probs
• Attract eos (intensify inflammation)

Thought that allergy/asthma may be a T cell disease