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POM > Immuno - Hypersensitivity > Flashcards

Immuno - Hypersensitivity Flashcards

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1
Q

What is the immune system role in hypersensitivity?

A
  • Over-reacting to harmless environmental particles: pollen, animal dander, drugs
  • Activation lead to inflammation cause pain & discomfort
  • Produce wide range of toxic molecules and protein result in tissue damage –> potentially fatal
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2
Q

What is an antigen?

A

A molecule/ar structure that can be recognised by antibody/adaptive immune system

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3
Q

What does it mean by requiring pre-sensitised immune system?

A

Having an existing adaptive immunological memory

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4
Q

How do we activate naive T-cells?

A

Encounter specific antigen for rapid proliferation (Clonal expansion)
Results in both effector and memory cells (differenciation)

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5
Q

How are different types of hypersensitivity triggered?

A

Depend on classes and subclasses of antibodies

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6
Q

How do we know what type of T-cells are generated?

A

Depends on what cytokines it’s exposed to

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7
Q

What are the 4 types of hypersensitivity?

A

Type I - Immediate/anaphylactic (allergen)
Type II - Antibody-mediated cytotoxic
Type III - Immune complex driven disease
Type IV - Delayed-type/ T-cell mediated

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8
Q

Which hypersensitivity reaction involve formation of antibody-antigen complex?

A

Type I-III

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9
Q

Which hypersensitivity reaction is initiated by T-cells?

A

Type IV

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10
Q

What does IgG do?

A

Activates complement & Fc receptor mediated phagocytosis?

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11
Q

What does IgA (dimer) do?

A

Cross mucosal epithelium

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12
Q

What does IgE do?

A

Mast cell degranulation

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13
Q

What classes of antibodies are there?

A

IgG, IgD, IgE, IgA (dimer connected by J chain) , IgM (pentamer connected with J chains & disulphide bonds)

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14
Q

What antibody mediates type I hypersensitivity?

A

IgE - usually only made in response to parasitic / potent venom
- Now produced against allergens (common multivalent environmental antigens)

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15
Q

What are examples of allergens?

A
  • Food (peanuts)
  • Plants (timothy grass/birch trees)
  • Animal dander (cats/dogs)
  • Drugs (penicillin/sulphonamides)
  • Insect products (bee venom/dust mites)
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16
Q

What test is used to test for Type I hypersensitivity?

A

Skin Prick test (expose skin to small amount of allergens)

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17
Q

What is a positive reaction for skin prick test?

A

Inflamed, raised tissue (aka Wheal & flare)

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18
Q

What is type I hypersensitivity? Examples?

A

Allergic reaction provoked by re-exposure to allergen

Asthma, allergic rhinitis, atopic dermatitis

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19
Q

What is the initial sensitization of type I?

A
  1. Generation of Type 2 CD4 T-cell (Th2) & B-cell follicular helper CD4 T-cell (Tfh)
  2. Tfh produces type II cytokines IL-4 & IL-13 (which promotes B cell to produce antigen specific IgE)
  3. IgE bound to surface of innate immune cells (mast cells & basophils - express high affinity IgE receptors)
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20
Q

What does Tfh do?

A

Produces type II cytokines IL-4 & IL-13 (which promotes B cell to produce IgE

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21
Q

What is the mechanism of sensitized Type I re-exposure to allergens?

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A

Allergen encountering bound IgE causes rapid crosslinking & degranulation of mast cell/basophils

Release of histamine (a host of cytokine):

  • recruit other cell
  • promote further Th2 differentiation + highly active smooth muscle contracting molecules (leukotrienes & prostaglandins)
22
Q

What are IgE receptors?

Study These Flashcards
A

Fc epsilon receptor I (FCER!)

23
Q

What are the phases of response in type I hypersensitivity?

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A
  1. Early phase (within mins od exposure) - bioactive small molecules produced by mast cells
  2. Later response (few hours) - recruitment of early inflammatory cells (eg neutrophils)
  3. Late response (3-4days) - lots of eosinophils recruited + Th2 cells present
24
Q

What are the uses of histamine and heparin (primary) Leukotrienes (secondary) ?

Study These Flashcards
A

Increase vascular permeability

Smooth muscle contraction

25
What do prostaglandins mediate?
Vasodilation, contraction of pulmonary smooth muscle, platelet aggregation
26
What are some examples of CD4 T-cells?
Th1 - produce molecules that promote control of intracellular pathogens Th2 - alllergic & anti-helminth reponse Tfh - B cell help in germinal centers Th17 - Inflammation Induced Treg - regulation, suppression of immune/inflammatory responses
27
What is type II hypersensitivity?
Destruction of cells by IgM & IgG binding to cells
28
What are the consequences of Type II hypersensitivity?
Tissue injury - Local & systematic inflammation - Cell depletion (loss of function/ balance in organ)
29
What are some causes of Type II?
- Mismatched blood transfusion - Haemolytic disease of the newborn - Graves disease - secretion of thyroid hormone - Immune thrombocytopenia - abs against platelet surface protein
30
How is Type II sensitized?
- Exposure to foreign antigen | - Aberrant response to self-antigen (IgM/G recognise)
31
What are the disease mechanism for type II?
1. Anti-receptor activity 2. Antibody dependent cell-mediated cytotoxicity (ADCC) 3. Classical activation of complement cascade
32
What is and how does ADCC work?
Antibody dependent cell-mediated cytotoxicity - Abs-ag complex bound by Fc receptors (expressed by granulocytes & NK cells) - cause direct lysis of target cell & release of inflammatory mediators, chemokines & cytokines
33
What does the complement cascade cause?
Inflammation Opsonisation Recruitment & activation of immune cells Lysis of cell
34
How does the complement cascade work?
Antibody recognised by complement components leading to the formation of MAC (membrane attack complex form pores) on cell surface leading to cell death (due to loss of osmotic integrity)
35
What is type III hypersensitivity?
Non-cell bound abs-(self)ag complex not cleared as deposited in vessel wall/tissue - promotes inflammation & tissue damage
36
What are the symptoms of Type III hypersensitivity?
``` Fever Rashes Joint pain Protein in urine Arthritis (joint) Glomerulonephritis (kidney) Vasculitis (blood vessel) ```
37
What are some autoimmune diseases involving Type III?
Rheumatoid Arthritis Multiple Sclerosis SLE - Systematic lupus erythematous
38
Give example of antibody-mediated diseases. Type III
``` Persistent infections (Hepatitis) Serum sickness - when given anti-serum to snake venom, Abs recognises it so 2nd exposure will cause inflammation ```
39
What is SLE?
Systematic Lupus Erythematous | - autoimmune disease that increases apoptosis + clearance of that material
40
What is the childhood form of SLE?
Juvenile-onset SLE (rare) | activates all components of innate & adaptive immune system
41
What is the mechanism for SLE?
1. Develop IgG against DNA/protein present in nucleus - forming persistent immune complex deposits & variety of pathologies 2. Antibody-nuclear antigen immune complex deposit in tissue cause local inflammation
42
What are the characteristics of SLE?
- Increase in apoptosis + clearance of it - Saturation of physiological process to remove lupus cluster in surface bleb of apoptotic cells AMPLIFIES immune exposure
43
What is type IV hypersensitivity?
Memory T-cell response promote inflammation
44
How is Type IV sensitized?
Naive T-cells presented to APC/DCs to generate memory T-cells
45
What is the most common type IV example?
Contact dermatitis (exposure to poison ivy)
46
What happens when exposed to poison ivy?
Urushiol molecule act as hapten (binds to skin protein) & presented to DCs --> T-cell clonal selection --> drives Th1 response - response is small, rarely result in antibody production
47
What happens when re-exposed to poison ivy?
Memory cells produce cytokines (Eg IFN-gamma) which promote pro-inflammatory activation of macrophages - Cause swelling + oedema + form blister-like lesions (cytotoxic T cell/Memory T-helper/macrophages/cytokines)
48
What other contact antigens also drive Th1 base inflammation?
Nickel salts / hairdyes / intracellular pathogens (Measles virus/ TB)
49
What other type IV reactions are there?
- Positive tuberculin skin test - measure previous exposure to TB (inject M.tb into skin) - Any memory T-cell capable of immune overreaction eg Asthma (Th2 --> produce soluble mediators promotes Bronchoconstriction) Inflammation & rejection of tissue graft - CD8 T-cells kill transplanted cells
50
How many types of hypersensitivity can contribute to pathology at the same time?
More than 1 ``` eg Asthma Type I (Generation after exposure - allergy) Type IV (Th2 --> produce soluble mediators promotes Bronchoconstriction) ```

POM (22 decks)

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