Hypersensitivity and Autoimmunity Flashcards Preview

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Flashcards in Hypersensitivity and Autoimmunity Deck (22):
1

Type I

- Allergy
- Inappropriate genesis of IgE
- IgE is directed against environmental antigens which may be airborne, ingested, injected or encountered through skin contact
- You need symptoms otherwise it's atopy

2

Reasons we get these allergic reactions

Combination of:
- interacting genetic factors
- environmental influences
- hormonal
- neurological influences

3

Pathogenesis of type I

- Allergen exposure
- Mast cell + allergen specific IgE
- Release of inflammatory mediators (mucosal oedema, capillary leakage, secretions, smooth muscle contraction, vasodilatation)

4

Type II

- Mediated by IgG or IgM antibodies which are directed against antigens found on the surface of cells or fixed within certain tissues
- Antigens can be exogenous or derived from self

5

Mechanisms of type II damage

- Complement-dependent lysis (complement activation)
- Fc receptor-mediated damage: Fc binding of immunoglobulin and stimulation of phagcytes
- Antibody-dependent cellular cytotoxicity (ADCC): actively lysing target cell
- Effect on target cell function: inhibition and stimulation

6

Type III

- Abnormal deposition of formed antigen (Ag)/antibody (Ab) complexes (immune complex formation) in tissues
- Can be exogenous or self

7

Type III - Immune complex formation

- Normal physiological process
- Complex formed to gain access to the blood stream and are kept soluble in the blood and transported to liver and spleen where the complexes are destroyed

8

What are the two ways that immune complexes can be formed?

- Physiological: normal, no symptoms or disease association
- Pathological: antigen factors, host response factors. 2 forms, serum sickness where immune complexes are deposited everywhere and arthus reaction where complexes form locally in tissues

9

Pathogenesis of type III

- Excessive or abnormal immune complex formation -> complement activation + recruitment of inflammatory cells -> tissue damage

10

Type IV

- Mediated by Th1 cells and the cytokine products (mostly interleukin-2 and gamma-interferon)
- Inappropriate response to inert environmental substances
- Reaction to infection with certain micro-organisms
- Usually delayed onset of about 48-72 hours

11

Why is there a type IV reaction from inert environmental substances?

- Too low a molecular weight to produce a substantial immune response
- Agent = HAPTEN and host protein is a CARRIER
- Carrier is necessary to produce antigenic bulk but the immune response is physically directed against the HAPTEN

12

Why is there a type IV reaction from micro-organisms?

- Happens when body finds it hard to destroy these environmental agents
- Micro-organisms such as mycobacteria don't do any harm but the immune response causes tissue damage.
- It evades, confounds or counteracts the immune response

13

Pathogenesis of type IV reactions

- Hapten + endogenous protein or microorganism
-> antigen uptake & presentation (HLA class II) -> Th1 antigen recognition/cytokine production -> inflammation

14

Mechanisms of immunological tolerance

- Central tolerance
- Peripheral tolerance

15

Central tolerance

- Arises through deletion of autoreactive T&B cells during cell maturation
- AKA positive and negative selection

16

Peripheral tolerance

- Inhibiting the activity of autoreactive cells which escape the central tolerance process

17

Why is recognition of self not always damaging?

- T cells recognise antigen which is complexed with self molecules
- Antibodies can recognise and bind portions of other antibodies which regulates their production and activity

18

What is autoimmune disease?

- Clinical disorders characterised by tissue or organ damage mediated through aberrant cellular and/or humoral immunological mechanisms
- Directed against autoantigens: can be throughout many tissues, or localised in specific organs or tissues

19

Factors involved in autoimmune disease

- Genetic factors
- Immune regulatory factors (defective tolerance induction, defective peripheral tolerance mechanisms)
- Hormonal factors (esp. female hormones)
- Environmental factors (infectious agents, sunlight, drugs, chemicals, nutritional factors)
- Misc (age, trauma, malignant disease)

20

What pathogenic mechanisms are involved in autoimmune disease?

Same as normal immune response:
- Cellular or antibody activity
- (auto)antibody activation of the complement-mediated inflammation
- Immune complex formation (Type III hypersensitivity)
- Recruitment of innate immune components (phagocytes/cytokines/NK cells)

21

Pathogenesis of autoimmune disease

Initiating event (environment) -> genetic factors e.g. particular HLA alleles -> breakdown of self tolerance -> autoreactivity -> humoral =/- cellular -> tissue damage

22

Organ-specific vs non-organ specific

- Organ specific: Hashimoto's thyroiditis
- Non-organ: Rheumatoid arthritis