Skin Immunology (Mainly Revision)

Question 1

Describe how keratinocytes in the epidermis help with the immune response

Answer 1

• Sense pathogens via cell surface receptors and help mediate an immune response.
– Keratinocytes can be activated by UV (sunlight) and sensitizers (eg. allergic contact dermatitis)
• Produce antimicrobial peptides (AMPs) that can directly kill pathogens.
– AMPs have been found at high levels in skin of patients with psoriasis
• Produce cytokines and chemokines.
– Recruit and regulate cells of the adaptive and innate immune system (eg. in psoriasis)

Question 2

Describe how langerhan’s cells help with the immune response

Answer 2

• A type of dendritic cell that intersperse with keratinocytes in the epidermis.
• The main skin resident immune cell.
• They are Antigen presenting cells (APC), characterized by the Birbeck granule.
– They act as sentinels in the epidermis.
– They process lipid Ag and microbial fragments and present them to effector T cells.
– They help to activate T cells.

Question 3

Mainly ___1____ cells are found in the epidermis. Whereas _____2_____ cells are found in the dermis.

Answer 3

1) CD8+ T

2) CD4 + and CD8+ T

Question 4

What type of T cell is associated with allergy/ atopy?

Answer 4

TH2

Question 5

Describe the difference between CD4 and CD8 T cells

Answer 5

CD4 are helper T cells. CD8 are cytotoxic T cells so they kill infected cells.

Question 6

Describe the difference between class 1 and 2 MHC molecules

Answer 6

Class 1 is found on all nucleated cells and presents to CD8 cells. Class 2 is found only on professional antigen presenting cells and presents to CD4.

Question 7

Describe type 1 hypersensitivity

Answer 7

Allergy- IgE mediated
Allergic response is driven by allergen binding to IgE coated mast cells. it can only occur after initial sensitisation. When IgE binds there is mast cell degranulation and release of histamine etc.

Question 8

Describe type 2 hypersensitivity

Answer 8

Antibodies are generated to self antigen. Autoimmune disease.

Question 9

Describe type 3 hypersensitivity

Answer 9

Immune complexes are deposited activating complement and inflammatory cells. e.g. hypersensitivity pneumonitis.

Question 10

Describe type 4 hypersensitivity

Answer 10

Delayed reaction. T cell mediated e.g. sarcoidosis and TB.

Question 11

In response to injury or infectious agent what do mast cells release? What does this result in?

Answer 11

Inflammatory mediators such as histamine. Inflammatory response is generated and neutrophils move into the wounded tissue by trans endothelial migration.

Question 12

How do tissue resident macrophages, mast cells and newly recruited neutrophils recognise extracellular pathogens? What does this result in?

Answer 12

By PAMPs (pathogen associated molecular pattern- these are LPS that normal cells don’t have). Recognition of PAMPs results in activation and killing through various mechanisms.

Question 13

Describe how dendritic cells form a link between the innate and adaptive immune system

Answer 13

Dendritic cells take up debris from pathogen containing PAMPs or antigen via phagocytosis. They then process display this material on MHC molecules. These activated dendritic cells leave the tissue and migrate to the lymph nodes where they can show the peptides to specific T and B cells which will then be activated.

Question 14

When are NK cells activated?

Answer 14

NK cells are activated by intracellular pathogens through absence of MHC-1 surface expression on pathogens.

Question 15

If there is a mixture of intracellular and extracellular pathogens what happens?

Answer 15

NK cells produce pro-inflammatory cytokine interferon gamma which acts on macrophages to turn them into superkillers. Interferon gamma also activated dendritic cells which then produce IL-12. IL-12 in turn activates more NK cells.

NOTE MACROPHAGES DO NOT PRODUCE INTERFERON GAMMA.

Question 16

Explain what interferon gamma favours T cell differentiation to

Answer 16

Favours TH1 cell differentiation this makes sense as these helper cells go to infected tissue and interferon gamma will be being produced due to presence of intracellular pathogens which you need good t cell response for.

Question 17

What 2 signals do B cells need to become activated?

Answer 17

Antigen and T helper cell signal

Question 18

What do B cells do?

Answer 18

Produce specific antibodies that circulate through out the body helping to kill and eliminate pathogens.

Question 19

Explain what class switching is

Answer 19

Cytokines produced by T cells induces class switching (of antibodies) therefore depending on the cytokine environment (which will be influenced by the type of pathogen) you get different Ig classes.

Question 20

Describe restoration to homeostasis

Answer 20

Some B and T cells become memory cells allowing quicker response to reinfection, these reside in the bone marrow. Macrophages switch behaviour and return to sweeping up dead cells. They also secrete anti-inflammatory cytokines to promote tissue repair and healing. Pro-inflammatory mediators, cytokines and acute phase proteins have a short half life.

Question 21

The immune response has a systemic effect on the liver what happens?

Answer 21

Activation of acute phase proteins which migrate into infected tissue. Also get activation of the complement system by mannose-lectin pathway and alternate pathway.

Question 22

What does CRP do?

Answer 22

CRP (C reactive protein) this protein primes certain bacteria for destruction by the complement system. It also has a prognostic role as can levels of it can give an indication of severity and duration of inflammation.

Question 23

Describe the complement system

Answer 23

This is a family of approximately 30 proteins that are produced in liver. They circulate in the blood and constitute 10% of serum proteins. The complement system, when activated, creates a cascade of chemical reactions that promotes opsonization, chemotaxis, and agglutination, and produces the MAC.

Question 24

Describe the MAC

Answer 24

The last five proteins in the complement cascade self-associate to form a membrane attack complex (MAC). MACS inserts themselves into pathogen membranes allowing extracellular salts and water to enter, causing the microbe to swell and burst. (OSMOTIC LYSIS)

Question 25

Which antibody is the first to be made in the immune response?

Answer 25

IgM

Question 26

Which antibody dominates in second exposure?

Answer 26

IgG

Question 27

What antibody is present in secretions?

Answer 27

IgA

Question 28

What antibody is important in allergic reactions?

Answer 28

IgE

Question 29

Which antibody has unknown function?

Answer 29

IgD

Question 30

What is erythema multiforme?

Answer 30

A hypersensitivity reaction with several triggers, most commonly skin infection (but also drugs)
Get Eruption initially of well circumscribed, round erythematous macules. The lesions Begin on the extremities and may spread to the trunk.
Lesions arise within a 24 hour period.

Question 31

What is steven johnson syndrome? (toxic epidermal necrolysis)

Answer 31

Very rare but potentially fatal hypersensitivity reactions involving the skin and mucous membranes.
Are ill before then get sudden develop of blistering skin rash and widespread erythema.