immunology 3: hypersensitivity reactions

Question 1

hypersensitivity reactions

Answer 1

type I = allergic reaction to foreign antigen

type II, III, IV = can be either to host or foreign antigen

Question 2

type I - immediate hypersensitivity reaction

Answer 2

allergic response only to foreign antigen

IgE mediated degranulation of mast cells + eosinophils releasing histamine

Th2 mediated

Question 3

type II - direct antibody mediated

Answer 3

direct antibody mediated

caused by antibodies reacting directly through binding with antigen present on the surface of cells or tissues, the binding then triggers complement cascade or activates macrophages

Question 4

type III - immune complex mediated

Answer 4

complexes of antibody antigen form and cause damage either at the site of formation or travel through circulation and cause damage elsewhere

Question 5

type IV - delayed hypersensitivity

Answer 5

T cell mediated and can 2 - 3 days to develop

Question 6

Type I pathway

Answer 6

allergen phagocytosed by dendritic cell which displays the allergen to Th2 cell. T cell will activate B cell.

B cell produces IgE

plasma cell secreting IgE, the IgE will bind to IgE receptor on a mast cell causing it to degranulate and histamine is released

histamine causes downstream cytokine (2 - 4 hours) and lipid mediator activation (minutes after repeat exposure)

Question 7

Type I allergy

Answer 7

following initial sensitisation where IgE is bound to IgE receptor on mast cell, a subsequent antigen exposure will cause the antigen to bind to the IgE bound to IgE receptor on mast cell triggering its degranulation

Question 8

Type II reaction to foreign antigens

Answer 8

reaction in response to foreign blood products i.e. haemolytic anaemia and rhesus incompatibility

Question 9

Type III reaction to foreign antigens

Answer 9

bacterial endocarditis

Question 10

Type IV reaction to foreign antigens

Answer 10

contact dermatitis

also observed in hard to clear pathogens
e.g. hep B + mycobacterium TB

Hep shuts down MHC 1

Question 11

autoimmunity

Answer 11

adaptive response to host components leading to chronic immune response

Question 12

tolerance

Answer 12

does not happen automatically and immunocytes need to be trained to not react to host proteins

Question 13

maintenance of tolerance

Answer 13

self reactive immature B cells are deleted in the bone marrow

anergic response in the periphery if B cell makes receptor that interacts with host protein by fas - fas ligand pathway on CD4+ T cells causing the B cell to become eliminated by apoptosis

self reactive T cells are deleted at the cortex/medulla in the thymus

mature self reactive lymphocytes are rendered unreactive (anargy) and deleted when they encounter self antigens

Question 14

breakdown in tolerance

Answer 14

some MHC subtypes are less able to present antigen to developing T cell so some self reactive T cells escape to periphery

Question 15

molecular mimicry and cross reaction of antibodies

Answer 15

cross reaction with host proteins for antibodies that are targeted towards antigens that are similar

e.g. streptococcus M protein —-> rheumatic fever
MS? diabetes?

antibody cross reacts with protein in cardiac muscle causing calcification of heart valves

Question 16

immune privilege and release of sequestered antigen

Answer 16

disruption of tissue barrier causes release of sequestered self antigen and activation of non tolerized cells

Question 17

superantigen

Answer 17

infection triggers massive T cell response causing polyclonal activation of autoreactive T cells causing their expansion

e.g. rheumatoid arthritis

Question 18

Goodpasture’s syndrome

Answer 18

antibodies directly bind to GBM protein found in glomerulus of the kidneys and trigger complement cascade and activation of macrophages

GBM = glomerular basement membrane

IgG autoantibodies bind to GBM triggering cc cascade and macrophages, producing cytokines and recruiting neutrophils and more B and T cells

results in: progressive glomerulonephritis i.e. progressive decrease in kidney function

inflammation, RBC present due to rupture of capillaries (C9) abnormal crescent shaped accumulation of cells in the urine surrounding glomerulus

Question 19

Type II hypersensitivity autoimmune diseases

Answer 19

goodpastures syndrome

autoimmune haemolytic anaemia

pemphigus vulgaris (epidermal cadherin)

acute rheumatic fever

Graves’ disease

myasthenia gravis

Question 20

Graves’ disease

Answer 20

more common causes of hyperthyroidism

antibody binding to receptor modifies the receptor behaviour causing it to produce too much metabolic hormones T3 and T4

Question 21

Type III autoimmune hypersensitivity

Answer 21

immune complexes of antigen and antibody are formed (precipitate) and are produces as part of normal immune response and cleared via complement cascade which opsonises them

in hypersensitivity the antigen is a host protein which will never be cleared or eliminated and result in chronic inflammatory reaction

the immune complexes can lodge in vasculature:
complement cascade occurs
neutrophils activated 
microthrombi formation
platelet aggregation

Question 22

Type III autoimmune examples

Answer 22

subacute bacterial endocarditis
> results in glomerulonephritis

mixed essential cryoglobulinemia
> systemic vasculitis

systemic lupus erythmatosus
> glomerulonephritis, vasculitis, arthritis

Question 23

SLE

Answer 23

IgG antibodies produces to self antigens most commonly:
antinuclear proteins
self DNA

e.g. UV damage where cells lyse and host DNA antigens, cytosolic proteins are exposed to immune population

characterized by malar (butterfly) rash

Question 24

type IV autoimmune hypersensitivity

Answer 24

driven by Th1 cells driving inflammatory response mediated by macrophages

cytokine responses

onset by provacations:
> physiological reaction to pathogen e.g. hep B
> in response to innocuous environment (nickel contact dermatitis)
> against autoantigens (diabetes)

hypersensitivity by both CD4 + CD8

Question 25

type IV autoimmune hypersensitivity examples

Answer 25

type 1 insulin dependent diabetes mellitus
rheumatoid arthritis
multiple sclerosis
celiac disease

Question 26

type 1 insulin dependent diabetes mellitus

Answer 26

autoreactive T cells attacking beta cells of the pancreas are expressed at low levels in the thymus

individuals with HLA DQ2 subtype who dont eliminate autoreactive T cells for beta cell of pancreas and tolerance is lost

a triggering infection will cause expansion of T cell population and autoreactive T cells will expand

Question 27

rheumatoid arthritis

Answer 27

inciting event unknown, perhaps superantigen

immune complex (autoantibodies) and complement precipitates on synovial lining
macrophages infiltrate synovium + activate
CD4 + CD8 infiltrate synovium
increase in HLA expression on synovial cells
Th1 cytokine secretion predominates leading to inflammation
infiltration of B cells

rheumatoid factor (IgM and anti IgG) binds to Fc portion of IgG

Question 28

multiple sclerosis (MBP)

Answer 28

specific antigen = Myelin basic protein (MBP)

CD4 + CD8 target MBP

demyelinating plaques = T cells and macrophages

relapsing remitting disease