Ch3 - Immunity

Question 1

IL-1 major activities and clinical relevance

Answer 1

Activate T cells and macrophages, promote inflammation

Implicated in septic shock, RA, and atherosclerosis

Question 2

IL-4 major activities and clinical relevance

Answer 2

Activation of lymphocytes, monocytes and IgE class switching
Relevant for mast cells ensitisation, allergy and nematode infections

Question 3

IL-5 major activities and clinical relevance

Answer 3

Differentiation of Eosinophils

MAbs against IL5 inhibit late phase eosinophilia in animal models

Question 4

IL-6 major activities and clinical relevance

Answer 4

Activate lymphocytes, differentiation of B cells, stimulation of acute phase proteins

Acts as growth factor in myeloma and mesangial proliferative glomerulonephritis

Question 5

IL-8 major activities and clinical relevance

Answer 5

Chemotaxis of neutrophils basophils and T cells

Levels increased in disease accompanied by netutrophilia

Question 6

TNF α major activities and clinical relevance

Answer 6

promote inflammation

MAbs beneficial in in RA and crohns

Question 7

What is the pathophysiology of chronic granulomatous disease?

Answer 7

failure to generate O2 in neutrophils and monocytes and inability to kill phagocytosed bacteria.

Question 8

Which cytokines are responsible for fever?

Answer 8

IL-1 IL6 and TNFα

Question 9

What are chemokines?

What are their receptors? What do they stimulate?

Answer 9

Substances that attract immune cells to areas where response is required.
G protein coupled receptors: activation results in extension of pseudopodia and therefore migration

Question 10

What are the key triggers for each of the classic, mannose binding lectin pathway and alternative pathway for the complement cascade?

Answer 10

Classic: immune complexes
Mannose binding lectin: lectin binds mannose groups in bacteria
Alternative: viruses, bacteria, fungi, tumour cells

Question 11

What are the 3 functions of the complement cascade?

Answer 11

Opsonisation, chemotaxis and lysis
Activate B cells and aid immune memory
Dispose of waste products

Question 12

What are TLRs and what is their relevance in innate immunity?

Answer 12

TLRs act as pattern recognition receptors
Bacterial LPS produced by gram -ve organisms and CD14 bind to TLR4 leading to activation of gene transcription producing innate immune responses.
TLR5: flagellal
TLR 2: microbial lipoproteins
TLR9: bacterial DNA

Question 13

TGF B major activities and clinical relevance

Answer 13

immunosuppression

Useful in MS and Myasthenia gravis

Question 14

GMCSF major activities and clinical relevance

Answer 14

promotes granulocytes and monocytes

used to reduce neturopenia in chemo etc.

Question 15

Interferon alpha major activities and clinical relevance

Answer 15

induces resistance to viral infection

Treats Kaposi sarcoma, chronic Hp b a nd C infection

Question 16

Interferon beta major activities and clinical relevance

Answer 16

Induces resistance to viral infection

Reduces frequency and severity of MS relapses

Question 17

What are the two key branches of acquired immunity?

Answer 17

Humoral: mediated by γ-globulin fraction of plasma proteins, major defense against bacterial infections
Cellular immunity: cytotoxic t cells attack and destroy cells bearing the antigen that activated, major defense against viral and fungal infections and tumors

Question 18

What are some examples of antigen presenting cells and where are they located?

Answer 18

Langerhan’s cells: skin
Dendritic cells: lymph nodes and spleen
macrophages and b cells can function as APCs

Question 19

Outline the pathway from APC ingestion of a protein to antibody production via B cells and Cell death via T cells

Answer 19

1. APC ingests antigen, presents with MHC2 on cell surface
2. MHC complex recognised by CD4 t cell
3. IL2 autocrine activates to multiply CD4
4. CD4 activates B cells via cytokines, and T cells via cytokines to produce antibodies in the former and to induce cell death via the latter

(MHC1 from APC can also activate the cytotoxic CD8 Ts)

Question 20

What is the function of IgA

Answer 20

localised protection in external secretions eg. intestine

Question 21

What is the function of IgG

Answer 21

complement activation

Question 22

What is the function of IgM

Answer 22

Complement activation

Question 23

What is the function of IgD

Answer 23

Antigen recognition by B cells

Question 24

What is the function of IgE

Answer 24

Reagin activity: releases histamine from basophils and mast cells

Question 25

List the contents of platelet granules and their key roles.

Answer 25

Granule 1: serotonin, ADP, secreted in response to platelet activation
Granule 2: secreted proteins
e.g PDGF: stimulates wound healing and vascular smooth muscle
e.g platelet activating factor: induces thromboxane and increases AA derivatives

Question 26

Name some severe combined immunideficiencies (SCID) and describe where they act.

Answer 26

MHCI and MHCII deficiency (between t cell precursor and CD4/CD8
Hyper IgM syndrome (between Naive B cell and plasma cells)
X glinked agammaglobulinaemia (between B cell precursor and Naive B cell)

Question 27

How do tacrolimus and cyclosporin work to prevent transplant rejection?

Answer 27

Prevent the dephosphorylation of NF-AT which is involved in the pathway between T cell receptor activation and gene transcription to release stimulatory cytokines.

Question 28

What is the role of thrombopoeitin? Where is it produced? What does high serum thrombopoeitin mean?

Answer 28

Produced in liver.
Facilitates megakaryocyte maturation into platelets.
When platelets are LOW, less is bound and more is available to stimulate production.

Question 29

What is the role of NFκB in the inflammatory response? What inhibits this?

Answer 29

Stimulated by cytokines, viruese and oxidants resulting in transcription of genes for inflammatory mediators. Inhibited by corticosteroids.

Question 30

What are the acute phase proteins and when are they highest?

Answer 30

INCREASE
CRP: day 0-5
Serum Amyloid A : day 0-7
Haptoglobin: day 7-14
Fibrinogen: day 10-14
C3: day 5-7

DECREASE
Albumin: day 5
Transferrin: day 5