Haematology and Immunology - Immunology

Question 1

What does the immune system do?

Answer 1

Defends host from invading pathogens

Divided into:

Innate
Fast, non-specific, no prior exposure
Barriers (Skin, mucosa, stomach acid, salivary enzymes)
Local inflammation (Macrophages & neutrophils)
Complement system
Pre-existing immunoglobulins

Adaptive
Slow and specific, requires prior exposure
Humoral (Immunoglobulins secreted by plasma B cells)
IgM, IgA, IgG, IgE, IgD
2 heavy chains, 2 light polypeptide chains liked by disuphide bonds.
The variation in class is from differences in heavy chain
Cellular
T cells attack pathogens and infected host cells, as well as +ve feedback to overall response
NK cells attack pathogens and cancer cells

Question 2

Discuss white blood cells

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Answer 2

Two lineages, both produced in bone marrow from haemopoetic stem cells

Myeloid
Neutrophils (attack bacteria/fungi)
Monocytes (migrate into tissues to become resident macrophages, such as hepatic Kupffer cells)
Basophils
Eosinophils (hyperensitivity and parasites)

Lymphoid
T Cells (carry cell surface receptors to recognise one antigen - >100,000,000 T lymphocytes in circulation)
Many subtypes
Cytotoxic CD8+ (T cell receptor recognises antigens presented on MHC, and destroys the infected cell)
Helper CD4+ (T cell receptor recognises MHC II carrying antigen, releases cytokines, activating B lymphocytes to differentiate to plasma cells & produce antibodies)
Memory
Suppressor

B Cells (Plasma cells produce antibodies & memory cells can be activated if an antigen is re-encountered)

Question 3

Characteristics, phases, and mediators

What is inflammation?

Answer 3

Most rapid element of the immune response

Four characteristics:
Calor - heat from increased blood flow and metabolic rate
Rubor - redness from vasodilation
Dolor - pain from inflammatory mediators
Tumor - swelling from increased capillary permeability

Three main phases
Hyperaemia - Localised vasodilation increases blood supply, with redness and rise in temperature
Exudation - Fluid, complement & cytokines leak into tissues causing swelling & pain
Emigration - White cells migrate along chemotactic gradients

Multiple mediators
Histamine/Leukotrienes
Released by mast cells & basophils
Increase capillary permeability
Trigger white cell migration

Kinin system
Kallikrein enzyme converts kininogen to bradykinin
Vasodilation and vascular permeabilitry

Neutrophils
Express adhesion proteins, stick to endothelium
Migrate along chemotactic gradients
Release platelet activating factor to trigger further inflammation

Tumour necrosis factor an interleukin 1b
Produced by multiple white cell lineages
Triggers vasodilation & leaky endothelium
Thought to be key player in septic shock syndrome

Complement
Plasma proteins produced by liver
Cascade response culminating in production of membrane attack complex (MAC)
Three pathways - classic, lytic, alternative
Opsonisation is the term used to describe action of some complement proteins, whereby they flag up target cells to be destroyed by the MAC

COX-2 and Eicosanoids
Production of pro-inflammatory prostaglandins

Question 4

What are the different types of hypersensitivity reactions?

Answer 4

Type 1 - Rapid IgE mediated reaction caused by cross linkage of mast-cell IgE. Widespread release of histamine and other vasodilatory agents. Includes anaphylaxis and asthma.

Type 2 - Antibody mediated - IgM or IgG react to antigens on cell surfaces. Includes blood transfusion reactions & haemolytic disease of the newborn

Type 3 - Immune complex mediated, IgG and complement form complexes and cause mast cells to degranulate & release histamine. Includes lupus and glomerulonephritis

Type 4 - Cell mediated, Memory T helper cells produce & release cytokines, activating macrophages. Includes contact dermatitis

Type 5 - Autoimmune, IgG and IgM autoantibodies against self-receptors. Includes Graves’ disease, myastehenia gravis

Question 5

What is the purpose of inflammation?

Answer 5

Ultimately to destroy the invading pathogen by
Making the tissue as inhospitable as possible with heat
Flooding the area with immune cells
Protecting the area against further damage (sensitising nociceptors & encouraging host to protect area)

Question 6

Explain & draw the complement cascade

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Answer 6

Classical and Alternative pathways activate C3
C3a leads to inflammation
C3b leads to opsonisation and continues the cascade to C5

C5a causes inflammation
C5b recruits C6/7/8/9 to form MAC

Membrane attack complex (disrupts phospholipids to cause osmotic cytolysis