Week 3 Hypersensitivities- Debiel

Question 1

What mechanism do the physical barriers of the skin use to prevent infection?

Answer 1

Dry
Regeneration
Low pH
High Salt

Question 2

What cells reside in the epidermis?

Answer 2

Langherhan cells (epidermis dendritic cell)

CD8+ TCells

Keratinocytes

Question 3

What cells reside in the Dermis?

Answer 3

Dermal Dendritic cells

Macrophages

CD4+ T cells (Th0)

Question 4

What molecules do TLRs on dendritic cells recognize?

Answer 4

PAMP (pathogen associated molecular patterns)

DAMP (damage associated molecular patterns)

Question 5

What does TLR 4 recognize?

Answer 5

LPS –> would suggest a gram neg bacterial invasion

Question 6

What does TLR 5 recognize?

Answer 6

Flagellin

Question 7

What do endosomal TLRs recognize? (TLR 9 and 3)

Answer 7

** used to recognize viral infections
TLR 9 = dsRNA
TLR 3 = unmethylated CpG

Question 8

What happens when an a TLR on a dendritic cells recognizes a PAMP?

Answer 8

1. dendritic cell engulfs
2. breaks down PAMP/cell
3. Presents fragments on MHCII
4. CD 4+ T Cells bind to MHC II (T cell receptor + CD4 protein binds the MHCII receptor on DC)
5. Th0 Cell now activated

Question 9

What is the first thing a Th0 cell will secrete?

Answer 9

IL-2

pro-proliferative and drives T cell growth and division

Question 10

What will happen if the dendritic cell interacting with the T-cell secretes IL-12?

Answer 10

it will drive Th0 to Th1 differentiation

Question 11

What do Th1 cells produce and what do those molecules do?

Answer 11

Th1 will produce:

More IL-2 = increase proliferation

IFN-gamma = continues to push more Th0 into Th1 (and blocks Th2), proinflammatory

TNF-beta = pro-inflammatory, activates macrophages

Question 12

What happens when the dendritic cell interacting with Th0 secretes IL-4? (or basophils nearby can also secrete IL-4)

Answer 12

Drives Th0 into Th2 differentiation

Question 13

What do Th2 cells produce and what do those molecules do?

Answer 13

Th2 cells produce:

IL-4 and IL-5: activates eosinophils and mast cells, and forces CLASS SWITCHING to IgE

IgE degranulates eosinophils and mast cells

IL-4 also drives Th2 differentiation and blocks Th1

Question 14

Type 1 hypersensitivity

Answer 14

AKA Immediate Hypersensitivity

• production of IgE Abs against foreign proteins that are common (pollen, animal danders, etc)
• IgE constant regions are bound to mast cells
• when allergen binds more than one antibody, stimulates degranulation of mast cell

Question 15

Type 2 hypersensitivity

Answer 15

AKA Antibody-mediated hypersensitivity

• Occurs when IgG or IgM antibodies are produced against surface antigens on cells of the body
• Abs can activate complement or facilitate the binding of NK cells

Question 16

Type 3 hypersensitivity

Answer 16

ALA Immune complex hypersensitivity

• formation of immune complexes in the circulation that are not adequately cleared by macrophages
• high levels of complex stick to walls and activate other immune cells

Question 17

Type 4 hypersenstivity

Answer 17

AKA Cell mediated hypersensitivity

• T-cells are primary effective cells
• T-cells active against posion ivy, nickel, exaggerated response to viral infection, delayed hypersensitivity
• Antigens stimulate larges levels of Th1 and Th17 which produce cytokines and increase inflammation

Question 18

What can classify an allergen?

Answer 18

Source
Route of exposure (important because it defines the ways in which the antigens are presented to the immune system)
and nature of specific protein

Question 19

What is IgE production dependent on?

Answer 19

Th2 cells

Th1 response will inhibit IgE production

Question 20

Atopic Dermatitis

Answer 20

Type 1 or 4

Highest levels of both specific IgE and total IgE

Question 21

Contact Hypersensitivity

Answer 21

Type 4

• occurs at the site of contact with an allergen
• Stage 1= Sensitization: first exposure to hapten, create memory T cells
• Stage 2 = Elicitation- recruitment, second exposure to hapten, recruitment of memory T cells and release of proinflammatory cytokines

Question 22

Tuberculin-type hypersensitivity

Answer 22

Type 4

- induced by CD4 T cells in responses to soluble antigens from a variety of organisms

Question 23

Granulomatous hypersensitivity

Answer 23

Type 4

• Clinically MOST IMPORTANT
• persistence of antigen leads to chronic T-cell activation
• Granuloma formation is driven by T-cell activation of macrophages, and is dependent on TNF
• many chronic diseases are granulomatous hypersensitivities

Question 24

What is a hapten?

Answer 24

small molecule that can elicit an immune response

• so small needs a carrier molecule like a protein to antagoinze the immune system
• lipophilic
  ex: nickel is a hapten