Clinical correlates immunology

Question 1

What 4 things can happen if the immune system goes wrong?

Answer 1

Hypersensitivity reactions (overreaction of immune system causing tissue damage)
Autoimmunity
Allergy
Immunodeficiencies

Question 2

What are the 4 types of hypersensitivity?

Answer 2

Type 1
Type 2
Type 3
Type 4

Question 3

What is type 1 hypersensitivity?

Answer 3

IgE mediated

Question 4

What is the mechanism for Type 1 hypersensitivty?

Answer 4

• Exposure to allergen
• allergen binds to IgE on mast cells
• IgE cross linking
• triggers “degranulation”—-> release of:
• Histamine—>vasodilation/ SM contraction
• Eosinophil/ neutrophil chemotactic agent—> increased inflammatory cells
• Proteases—> tissue damage
• Other mediators

Question 5

Examples of type 1 hypersensitivity

Answer 5

Eczema
Asthma
Hey fever
Anaphylaxis

Question 6

What is type II hypersensitvity?

Answer 6

Cytotoxic/ antibody (IgM or IgG) mediated

Question 7

Mechanism for type II hypersensitivity (first mechanism)

Answer 7

Antibodies (either made by own immune system or from another source) bind to target antigen on cell surface—> triggers one of three mechanisms:
1. Cytotoxic T cells bind to Ab–>release perforin/ granzymes —-> apoptosis of cell

Question 8

Mechanism for type II hypersensitivity (second mechanism)

Answer 8

2. Activate complement pathway:
   - Complement binds to antibodies (opsonisation)—> phagocyte binds —-> cell is phagocytosed
   - Complement forms membrane attack complex—> osmotic swelling of cell—> cell lysis
   - Complement acts as chemotactic agent—> increased inflammatory cells in tissue—> tissue damage

Question 9

Mechanism for type II hypersensitivity (3rd mechanism)

Answer 9

3. Antigen is a cell surface receptor—> Ab activates/ blocks normal receptor

Question 10

Examples of Type II hypersensitivity?

Answer 10

Graves disease
Blood transfusion reactions

Question 11

What is type III hypersensitivity?

Answer 11

Immune complex mediated

Question 12

Mechanism for type III hypersensitivity

Answer 12

• Increased antibody production in response to antigen
• antibodies enter blood and bind to soluble antigens
• immune complexes form
• immune complexes get lodged in basement membrane of blood vessels
• activates the complement cascade:
• Increased vascular permeability—> oedema
• Chemokines—> increased neutrophils in the area —> local damage to tissue

Question 13

Examples of type III hypersensitivity

Answer 13

Lupus
Rheumatoid arthritis

Question 14

What is type IV hypersensitivity?

Answer 14

Cell mediated/ delayed

Question 15

What are the 2 parts of the mechanism for type IV hypersensitivty?

Answer 15

Sensitisation
Once sensitised

Question 16

What is sensitisation?

Answer 16

• First exposure to antigen
• engulfed by antigen presenting cells
• antigen “presented” to naive CD4 positive T cells
• naive cells mature into TH1 cell

Question 17

What happens once sensitised?

Answer 17

-Repeat exposure to antigen
- Antigen binds to sensitised TH1 cell
- Cytokines released
- Activation of macrophages
- Release proinflammatory cytokines/ enzymes
- Activation of cytotoxic T cells
- Direct cellular damage

Question 18

Examples of type IV hypersensitivity

Answer 18

• Coeliac disease
• Type 1 diabetes

Question 19

Cause of autoimmune diseases

Answer 19

• Arise due to type II/III/IV hypersensitivity reactions against self antigens

Question 20

What is tolerance?

Answer 20

The process by which self reactive B & T cells are killed/ inactivated. Two types
- Central
- Peripheral
In autoimmune conditions tolerance has failed

Question 21

What is central tolerance?

Answer 21

in bone marrow/ thymus when self lymphocyte is maturing

Question 22

What is peripheral tolerance?

Answer 22

if lymphocyte escapes into circulation/ other tissues

Question 23

General clinical presentations for autoimmune diseases

Answer 23

• More common in younger women
• Overlap between other autoimmune conditions
• Mixed multifactorial environmental/ genetic aetiology
• Often treated with immunosuppression

Question 24

Common examples of autoimmune diseases

Answer 24

• Lupus (antibodies against substances from nucleus e.g. anti dsDNA)
• Type 1 diabetes mellitus (antibodies against islet cells in pancreas)
• Graves disease (thyroid stimulating antibodies)

Question 25

Causes of allergy

Answer 25

Arise due to type I hypersensitivity reactions against certain exogenous antigens (allergens)

Question 26

Examples of allergic reactions and their causes in increasing severity

Answer 26

Hay fever (allergic rhinitis)= pollen Eczema (atopic dermatitis)= soaps/ detergents Allergic asthma= dust/ animals Hives (urticaria)= food/drugs/ insect bites Angioedema= '' Anaphylaxis= ''

Question 27

What is the Atopic triad?

Answer 27

When asthma, eczema and hay fever occur in the same patient

Question 28

What is the atopic march?

Answer 28

describes natural history of these conditions

Question 29

What is anphylaxis?

Answer 29

- Severe life threatening allergic reaction Symptoms: - Low bp (vasodilation)- shock - Sob (smooth muscle constriction) - Loss of consciousness - ± angioedema, hives

Question 30

What is immunodeficiency?

Answer 30

- When a person has an absent or defective immune response - Can be classified as either Primary or secondary

Question 31

What is primary immunodeficiency?

Answer 31

Genetic - Di George syndrome (small or absent thymus) - SCID (Severe combine immune deficiency)= lots of problems inc inability for T cells to survive - CVID (common variable immune deficiency)= low antibodies

Question 32

What is secondary immunodeficiency?

Answer 32

Acquired - Malnutrition - Drugs (Chemo, anti- rejection drugs, to treat autoimmune conditions, steroids) - HIV/AIDS

Question 33

How does HIV/ AIDS cause immunodeficiency?

Answer 33

- Infects CD4+ T helper cells - Takes over function of T cell to enable viral replication - T cell function (& CD4 count) falls with time - Increased risk of opportunistic infections

Question 34

Vaccine principles

Answer 34

- Aim to "Teach" the immune system to create specific memory cells without needing to suffer disease - Means if exposed to pathogen= no/milder disease develops - Variable length of protection e.g. Flu vaccine

Question 35

What are the 3 vaccine types?

Answer 35

1. The whole microbe - inactivated/ killed e.g. hep A - Live- attenuated e.g. MMR - Viral vector e.g. AstraZeneca COV 2. Part of the microbe - Subunit/acellular e.g. pertussis 3. Genetic material - mRNA e.g. pjizer COV

Question 36

What are the effects of vaccines?

Answer 36

- Herd immunity - Less deaths in those who are vaccinated - Decreased rate of infection in cases where vaccine is used

Question 37

Why don't we use vaccines sometimes?

Answer 37

- Patient preference - Live viruses in immunocompromised patients - Allergy to ingredient in vaccine

Question 38

What is present on an APC?

Answer 38

MHC or human leukocyte antigen (HLA) complex

Question 39

What are HLA & their relevance?

Answer 39

-HLA Proteins have evolved to be very polymorphic, to ensure that at least some individuals within a population will be able to recognise antigens produced by virtually any microbe, and prevent extinction level pandemics - As HLA are so diff, means lots of opportunities to recognise the antigens produced by other peoples organs

Question 40

What different types of HLA are there?

Answer 40

- Class I, HLA= A, B, C - Class II, HLA= DR, DQ & DP A, B & DR= most important in determining a good organ match

Question 41

What determines our HLAs?

Answer 41

- You inherit your HLA from your parents, three from mother and three from father - They are expressed in a co- dominant manner - The result is a total of six markers, which are identified by different numbers

Question 42

What is a good match?

Answer 42

- The more markers that match between donor and recipient, the better the outcomes - Perfect match (0,0,0)= VERY RARE - Usually aim for 2 or less mismatches but it depends on circumstances - Parents usually mismatch half (1-1-1= total 3)

Question 43

What do patients still need with 0-0-0 mismatch?

Answer 43

- To be matched for ABO blood groups - To be on life- long immunosuppression drugs