Week 1 - E - Skin immunology (Langerhans/T.cells/ M.H.C), Bacterial Virulence - Toxic shock/P.V.L/Necrotising fasciitis

Question 1

What is the front-line defence between us and pathogens, chemical insults and physical trauma?

Answer 1

This would be the skin acting as an immunological system

Question 2

The immune system is composed of innate and adaptive components Which is first line? Which is specific? Which is memory?

Answer 2

The innate immune system is the non-specific first line immune defence (eg stratum corneum of skin) The adaptive immune system is the highly specific due to memory, self-limiting immune defence

Question 3

Describe how the keratin layer contributes to the immune defence?

Answer 3

This provides a tough, lipid rich (due to lamellar organelles secreting the high lipid content defence) phsyical barrier It is formed by terminal differentiation of keratinocytes to corneocytes

Question 4

The structural and functional cells of the epidermis are the keratinocytes What are the three main ways in which keratinocytes play an immunological role?

Answer 4

* They sense pathogens via cell surface receptors and help mediate an immune response * They produce antimicrobial peptides that can directly kill pathogens * They produce cytokines and chemokines

Question 5

What is the type of dendiritic cell found in the epidermis that acts as an antigen presenting cells? - they are the main skin resident immune cell What layer of the epidemis are they found in? What characterises the Langheran cell under microscope?

Answer 5

The main skin resident ummune cells are langerhans cells found in the prickle cell layer of the epidermis They are antigen presenting cells characterise by the Birbeck granule

Question 6

What cells do the langerhans cells present the antigen to?

Answer 6

They process lipid Ag and microbial fragments and present them to effector T cells. They help to activate T cells.

Question 7

Healthy skin contains a larger number of T lymphocytes (T cells) in both the epidermis and dermis Which type are found in the dermis and epidermis?

Answer 7

Mainly CD8+T cells are found in the epidermis (cytotoxic t cells) CD4+ and CD8+ T cells are found in the dermis

Question 8

Which type of CD4 cells assoicated with inflammation are associated with conditions such as psoriasis and atopic dermatitis?

Answer 8

Psoriasis associated with Th1 cells Atopic dermatitis associated with Th2 cells Both psoriasis and atopic dermatitis associated with Th17 cells

Question 9

Where are t cells produced? Where are they sensitised? They are the basis of cell-mediated immunity

Answer 9

T cells are produced in the bone marrow and sensitized in the thymus - many subgroups exist

Question 10

T Lymphocytes are one of the most important groups of effector cells of adaptive immunity. There are a lot of different subgroups of lymphocytes Helper T cells are known as CD4+ cells, and cytotoxic T cells are known as CD8+ cells. What is the role of Th1 and Th2 cells? (subgroup fo CD4+ cells) What is the role of cytotoxic T cells?

Answer 10

Th1 cells activate macrophages to destroy microorganisms Th2 cells help B cells to make antibodies CD8 T cells can ill infected cells directly

Question 11

Ag recognition and T cell activation involve interaction with the T cell receptor (TCR) and the Major Histocompatibility Complex (MHC). Which MHC class presents to CD4+ and CD8+ T cells?

Answer 11

MHC Class I presents to CD8 + T cells (cytotoxic T cells) MHC Class II presents to CD4+ T cells (T helper cells)

Question 12

The human MHC is also called the HLA (human leukocyte antigen) complex (often just the HLA) Which chromsome is the HLA located on?

Answer 12

HLA are found on chromosome 6

Question 13

What does virulence mean?

Answer 13

Virulence is the capacity of a microbe to cause damage to the host

Question 14

What is a virulence factor?

Answer 14

A virulence factor is a molecule produced by pathogens that contribute to the pathogenicity of the organism and enable colonization of the host

Question 15

Virulence factors are molecules produced by bacteria, viruses, fungi, and protozoa that contribute to the pathogenicity of the organism and enable colonization of the host There are 5 different virulence factors. Name them Which virulence factors are responsible for the variation in virulence within and between microbe species?

Answer 15

Adhesin Invasin Impedin Aggresin Modulin Adhesin, impedin and aggresin are the factors responsible for the variations in virulence factors within and between species

Question 16

What is the function of the different virulence factors? * Adhesin * Invasin * Impedin * Aggresin * Modulin

Answer 16

Adhesin - enables binding of the organism to host tissue Invasin - enables the organism to invade a host cell/tissue Impedin - enables the organism to avoid host defence mechanisms Aggresin - causes damage to the host directly Modulin - induces damage to the host indirectly Adhesin, impedin and aggresin are the factors responsible for variation in virulence within and between species

Question 17

What organisms can cause toxic shock syndrome? Which organism produces TSST?

Answer 17

Toxic shock syndrome can be caused by both staph auerus and strep pyogenes In both TSS (caused by S. aureus) and TSLS (toxic shock-like syndrome) (caused by S. pyogenes), disease progression stems from a superantigen toxin. The toxin in S. aureus infections is TSS Toxin-1, or TSST-1

Question 18

Why is toxic shock syndrome toxin known as a superantigen?

Answer 18

This is because the toxin activates 1in5 T cells instead of the normal 1in 10,000 therefore having a massive effect

Question 19

What does the mass activation of the T cells cause?

Answer 19

Causes the massive release of cytokines and an inappropriate immune response

Question 20

What is the diagnostic criteria for toxic shock syndrome?

Answer 20

* Fever >39 degrees * Diffuse macular rash - looks like sunburn and desquamation - shedding of the top layer of skin * Hypotension /= 3 organ systems involved - liver, blood, renal, mucous membranes, GI, CNA

Question 21

What are risk factors for toxic shock syndrome?

Answer 21

Risk factors include the use of very high absorbent tampons or having an infection Occurs rapid onset

Question 22

What is the treatment of TSS?

Answer 22

Intravenous fluids, antibiotics, drainage of any abscesses

Question 23

Multiple virulence factors make staph aureus a highly effective pathogen What is the cytotoxin associated with highly virulent strains of Staph. aureus which has direct toxicity to leukocytes? (white blood cells)

Answer 23

This would be panton-valentine leukocidin

Question 24

What is rapidly progressive infection of the deep fascia causing necrosis of the subcutaneous tissue known as? What can cause it?

Answer 24

This is necrotizing fasciitis - flesh eating disease Most commonly caused by strep pyogenes (group A beta haemolytic strep) Can be caused by staph aurues (linked to panton valentine leukocidin (PVL)

Question 25

What are the symptoms of necrotising fasciitis?

Answer 25

Severe pain and often little to see on skin sruface Can see blistering and necrotic skin Swelling of the skin will feel firm to touch Crepitus - feeling of almost bubble wrap under the skin

Question 26

How is it diagnosed? What is the treatment of necrotising fasciits?

Answer 26

Tissue cultures rather than wound swabs should be performed Urgent debridement and IV antibiotics