Clinical correlates immunology Flashcards
What 4 things can happen if the immune system goes wrong?
Hypersensitivity reactions (overreaction of immune system causing tissue damage)
Autoimmunity
Allergy
Immunodeficiencies
What are the 4 types of hypersensitivity?
Type 1
Type 2
Type 3
Type 4
What is type 1 hypersensitivity?
IgE mediated
What is the mechanism for Type 1 hypersensitivty?
- 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
Examples of type 1 hypersensitivity
Eczema
Asthma
Hey fever
Anaphylaxis
What is type II hypersensitvity?
Cytotoxic/ antibody (IgM or IgG) mediated
Mechanism for type II hypersensitivity (first mechanism)
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
Mechanism for type II hypersensitivity (second mechanism)
- 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
Mechanism for type II hypersensitivity (3rd mechanism)
- Antigen is a cell surface receptor—> Ab activates/ blocks normal receptor
Examples of Type II hypersensitivity?
Graves disease
Blood transfusion reactions
What is type III hypersensitivity?
Immune complex mediated
Mechanism for type III hypersensitivity
- 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
Examples of type III hypersensitivity
Lupus
Rheumatoid arthritis
What is type IV hypersensitivity?
Cell mediated/ delayed
What are the 2 parts of the mechanism for type IV hypersensitivty?
Sensitisation
Once sensitised
What is sensitisation?
- First exposure to antigen
- engulfed by antigen presenting cells
- antigen “presented” to naive CD4 positive T cells
- naive cells mature into TH1 cell
What happens once sensitised?
-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
Examples of type IV hypersensitivity
- Coeliac disease
- Type 1 diabetes
Cause of autoimmune diseases
- Arise due to type II/III/IV hypersensitivity reactions against self antigens
What is tolerance?
The process by which self reactive B & T cells are killed/ inactivated. Two types
- Central
- Peripheral
In autoimmune conditions tolerance has failed
What is central tolerance?
in bone marrow/ thymus when self lymphocyte is maturing
What is peripheral tolerance?
if lymphocyte escapes into circulation/ other tissues
General clinical presentations for autoimmune diseases
- More common in younger women
- Overlap between other autoimmune conditions
- Mixed multifactorial environmental/ genetic aetiology
- Often treated with immunosuppression
Common examples of autoimmune diseases
- 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)
Causes of allergy
Arise due to type I hypersensitivity reactions against certain exogenous antigens (allergens)
Examples of allergic reactions and their causes in increasing severity
Hay fever (allergic rhinitis)= pollen
Eczema (atopic dermatitis)= soaps/ detergents
Allergic asthma= dust/ animals
Hives (urticaria)= food/drugs/ insect bites
Angioedema= ‘’
Anaphylaxis= ‘’
What is the Atopic triad?
When asthma, eczema and hay fever occur in the same patient
What is the atopic march?
describes natural history of these conditions
What is anphylaxis?
- Severe life threatening allergic reaction
Symptoms: - Low bp (vasodilation)- shock
- Sob (smooth muscle constriction)
- Loss of consciousness
- ± angioedema, hives
What is immunodeficiency?
- When a person has an absent or defective immune response
- Can be classified as either Primary or secondary
What is primary immunodeficiency?
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
What is secondary immunodeficiency?
Acquired
- Malnutrition
- Drugs (Chemo, anti- rejection drugs, to treat autoimmune conditions, steroids)
- HIV/AIDS
How does HIV/ AIDS cause immunodeficiency?
- 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
Vaccine principles
- 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
What are the 3 vaccine types?
- The whole microbe
- inactivated/ killed e.g. hep A
- Live- attenuated e.g. MMR
- Viral vector e.g. AstraZeneca COV - Part of the microbe
- Subunit/acellular e.g. pertussis - Genetic material
- mRNA e.g. pjizer COV
What are the effects of vaccines?
- Herd immunity
- Less deaths in those who are vaccinated
- Decreased rate of infection in cases where vaccine is used
Why don’t we use vaccines sometimes?
- Patient preference
- Live viruses in immunocompromised patients
- Allergy to ingredient in vaccine
What is present on an APC?
MHC or human leukocyte antigen (HLA) complex
What are HLA & their relevance?
-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
What different types of HLA are there?
- Class I, HLA= A, B, C
- Class II, HLA= DR, DQ & DP
A, B & DR= most important in determining a good organ match
What determines our HLAs?
- 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
What is a good match?
- 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)
What do patients still need with 0-0-0 mismatch?
- To be matched for ABO blood groups
- To be on life- long immunosuppression drugs
