When the immune system goes wrong

Question 1

Primary immunodeficiency diseases

Answer 1

Rare disorders caused by an inherited flaw in the immune system that increases susceptibility to infection.
Examples -
SCID
Di George syndrome
X-linked agammaglobinaemia
Congenital neutropenia

Question 2

SCID

Answer 2

Severe combined immunodeficiency
A group of disorders resulting in an inability to make B or T cells, need bone marrow transplant or gene therapy.

XSCID - lack of IL-2 receptor gamma subunit, important for IL-2 signalljng and T cell proliferation

Adenosine deaminase deficiency - results In an accumulation of toxic levels of deoxyadenosine.

XSCID-type disease - JAK3 deficiency, important for IL-2 signalling and T cell proliferation

Question 3

Di George syndrome

Answer 3

Caused by genetic mutations on the long arm of chromosome 22.
Defective/abscent thymus gland
Susceptible to recurrent infections and often have physical abnormalities (wide spaced eyes, low set ears, small receding jaw bone)
Particularly susceptible to viral/fungal infection
Poor prognosis

Question 4

X-linked agammaglobinaemia

Answer 4

Caused by a mutation of gene that encodes Bruton's tyrosine kinase.
Present in X chromosome
Patients fail to make mature B cells
Treatment with pooled gammaglobulin
Usually not fatal

Question 5

Congenital neutropenia

Answer 5

Abnormally low number of neutrophils made jn bone marrow due to genetic defect
Individuals are prone to infections which may be fatal if not treated
Not usually fatal

Question 6

Acquired immunodeficiency diseases

Answer 6

Result in reoccurring opportunistic and often severe infections.
Goal of treatment is to control infections
Infections are treated with antibiotics, sometimes on a regular basis as preventative treatment
Examples -
AIDs
Leukaemia
Malnutrition is a common side effect
Drugs can induce immunodeficiency as can radiotherapy, normally due to depletion of haematopoietic stem cells in bone marrow

Question 7

AIDs

Answer 7

Caused by HIV retrovirus

Attacks CD4 cells

Question 8

Leukaemia

Answer 8

Describes several cancers of the blood/bone marrow

Characterised by abnormally high proliferation of immature white blood cells

Question 9

Over reaction of the immune system

Answer 9

Adaptive responses are sometimes provoked by antigens not associated with infectious agents.
This can cause tissue damage and / or disease.

Question 10

Hypersensitivity reactions

Answer 10

Harmful immune reactiosn often made in response to inherently harmless, known environmental antigens.
Four classes
Type I (immediate)
Type II (cytotoxic)
Type III (immune)
Type IV (delayed)

Question 11

Type I hypersensitivity

Answer 11

Reaction provoked by reexposure to an allergen.
Eliciting agents include - pollen,dust,food.
Associated diseases are - asthma atopy, anaphylaxis.
Initial exposure - IgE synthesizing plasma cells and memory cells are made, individualmis not sensitized.
Subsequent exposure - large increase in allergen responisve IgE, release of histamine and other mediators, promotes eosinophil and TH2 cell recruitment. Inflammatory response.
Effects of mast celk activation depends on location;
D and V if in gut
Hives if in skin
If systemic then anaphylaxis.

Question 12

Autoimmune reactions

Answer 12

Harmful immune reactions usually made in response to self auto-antigens.
Type II - antibody vs cell/matrix, rhesus antigens are the auto-antigen, results in red blood cell destruction.
Type III - immune complex, nuclear componants are the auto-antigen, results in potentially fatal embolisms (systemic lupus)
Type IV - T cell mediated, the auto-antigen is and unknown B cell (diabetes) or synovial antigen (RA). Results in destruction of cells.

Question 13

Pathogenesis of RA

Answer 13

Triggered by autoimmune reaction
Leads to clonal expansion of autoreactive TH1 cells.
Monocytes are recruited to synovium
Fibroblasts and macrophages secrete pro-inflammatory cytokines (TNFa, IL-1, IL-6)
Secretion on proteases causes cartilage and bone erosion.

Question 14

Autoimmune haemolytic anaemia

Answer 14

RBCs opsonised with autoIgG and IgMs versus cell Rh antigen have two fates -
IgG - phagocytosis and destruction of opsonised cells by macrophages
IgM - triggering of complement pathway leading to opsonisation and haemolysis
Uptake and clearance events occur predominantly in the spleen.

Question 15

Pathogenesis of type I diabetes mellitus

Answer 15

Auto-antigen specific for pancreatic B-cells
Effector T cell recognises peptides from B-cell specific protein and kills the B-cell.
Now no insulin can be made.