Hypersensitivity and Autoimmunity Flashcards Preview

B4W3 > Hypersensitivity and Autoimmunity > Flashcards

Flashcards in Hypersensitivity and Autoimmunity Deck (41):
1

What is the lifespan of a neutrophil? 

1-2 days 

2

What is hypersensitivity and what are the four types which exist? 

Hypersensitivity is an unwanted immune response.

It can be caused by infection, environmental substances, self-antigens.

A image thumb
3

Broadly, what are the hypersensitivity reactions? 

II, III, IV - diseases characteristic of autoimmune disease. 

A image thumb
4

What are allergens? 

-Antigens which cause allergy are called allergens.

- They are small proteins

- There is no clear feature shared by all allergens but many are a specific type of enzyme called a protease.

- Exposure is generally through inhalation, ingestion or administered as drugs.

- Most allergens promote a Th2 immune response.  

5

What are the characteristics of a type 1 hypersensitivity reaction? 

IgE & The Mast Cell 

A image thumb
6

What is Allergy and Atopy? 

- Allergy only occurs as a result of repeated exposure to an allergen which generates an IgE mediated immune response. 

- Atopy is the term used to describe a predisposition for an IgE mediated immune response. 

A image thumb
7

How does IgE bind to mast cells?

- IgE binds to mast cells via the IgE receptor (FceR1) 

 

- IgE not the most abundant antibody, but performed and loaded onto Mast cell makes this a really potent response (pre loaded, increases the half-life of IgE) 

A image thumb
8

What is the mechanism of allergy? 

- Cross-linking of two IgE molecules on the surface of mast cells results in granule release and the release of mediators of inflammation.

- Immediate reaction

- Late reaction

- Mediators of inflammation: Histamine, herparin and tripdase

The mast cells don't stop there - they are capable of stimulating leukotrienes and producing cytokines 

A image thumb
9

What is immediate I hypersensitivity reaction? 

Characterised by release of mast cell mediators: 

Histamine:

- Causes smooth muscle contraction of lungs, gut and blood vessels promoting oedema:

- Acts as chemoattractant to other WBCs - particularly neutrophils and eosinophils.

- Causes skin itching.

Cytokines:

- Pro-inflammatory induce inflammation (e.g. TNFalpha)

Enzymes e.g. Tryptase

- Activate complement

Leukotrienes - bronchial and gut contraction and chemotaxis and eosinophils and neutrophils

Prostaglandins - vasodilation, increased vascular permeability and constriction of gut and bronchial smooth muscle.

Th2 cytokines - IL-4 to activate Th2 cells and Il-3 and IL-5 to induce eosinophil activation. 

A image thumb
10

What is the late hypersensitivity reaction? 

- Occurs hours after exposure

- Migration of leukocytes espcially eosinophils.

- Eosinophils release peroxidase and other mediators which cause further tissue damage 

A image thumb
11

What are the effects of mast cell activation? 

A image thumb
12

What is allergic rhinitis? 

Treatment: 

- Reduced exposure

- Intranasal corticosteroids

- Anti-histamines

- Some instances: immunotherapy

A image thumb
13

What are Leukotrienes? 

Leukotrienes are a family of inflammatory mediators produced by leukocytes by the oxidation of arachidonic acid and EPA. 

14

Explain the pathology of asthma 

- Histamine plays less of a role in asthma than other allergic diseases.

Treatment:

Reliever Inhalers (Salbutamol - B2 agonist)

- Preventatibe Inhalers - corticosteroids

- Leukotriene receptor antagonists

- Theophylines (inhibit leukotriene synthesis) 

15

What is allergic eczema? 

- Itchy, dry, red and cracked skin.

- Barrier dysfunction - protein called filaggrin

- Treatment:

- Reducing Scratching

- Emollients (moisturising)

- Topical corticosteroids

 

A image thumb
16

What is Urticaria? (T1 hypersensitivity)

- Raised red itchy bumps or wheals

- Response to histamine release within the skin

- Treatment: 

- Trigger avoidance

- Anti-histamines

- Corticosteroids

- Leukotriene receptor antagonists

- Ciclosporin

- Omalizumab (anti-IgE therapy) 

17

What is anaphylaxis (T1 hypersensitivity)

- Systemic response to an allergen via any exposure route

- Rapid synthesis of prostaglandins and leukotriene

- Systemic vasodilation and increased vascular permeability

- Fluid enters extravascular space

- Fall in blood pressure

- Severe bronchiole constriction, oedema and shock

- Similar to systemic inflammation

- Anaphylaxis should always be treated as a medical emergency

18

What is Type II hypersensitivity? 

- Antibody mediated - IgG or IgM 

- Cytotoxicity to tissues:

1. Antibody dependent cellular cytoxicity (ADCC)

2. Complement dependent cytotoxicity (CDC)

- Cellular receptor modifying (Type V hypersensitivity)

 

Can be a reaction to cause cytotoxicity to tissues, or can also be to modify cell/receptor function.

In Type II hypersensitivity, the antibodies produced by the immune system bind to the patient's own cell surfaces.

These cells are recognised by macrophages or dendritic cells, which act as antigen-presenting cells. This causes a B cell response, wherein antibodies are produced against the foreign antigen.

 

An example of Type II hypersensitivity is ABO blood incompatibility.

A image thumb
19

What is Rhesus Disease/Haemolytic disease of the newborn? 

- Baby with big spleen & abdomen

- High levels of bilirubin, rash on face due to platelet response

- A Rh D- mother if exposed to RhD+ RBC from a foetus will develop anti-D IgG antibodies - sensitisation.

- In subsequent pregnancies IgG can cross the placenta to induce haemolysis of foetal RBC - Rhesus disease of the newborn. 

 

20

Explain the process of drug induced haemolytic anaemia

- Antibodies can also target our own cells - this is seen in the case of drug induced haemolytic anaemia

- Binding of drugs to cells can induce an immune response

- Antibodies recognise drug in combination with cells

- Drug acts as immunological hapten.

e.g. penecillin 

21

Explain Goodpasture Syndrome

- IgG antibodies recognise collagen within the kidney basement membrane

- IgG binding to basement membrane results in complement activation 

- Treatment:

- Oral immunosuppressants

- Plasmpheresis

- Complement + Subsequent activation

 

22

Explain Myasthenia Gravis

 

- Antivodies block the acetylcholine receptor at neuromuscular junctions preventing nerve impulse transmission.

- Presents at muscle weakness especially of the eyes and face but all muscles can be affected

23

Treatment: 

- Pyridostigmine - blocks acetylcholinesterase which suppresses AcH

- Corticosteroids

- Immunosupressants

- Thymectomy

- Biologics - B cell depleting therapy 

24

What is Graves Disease 

- Antibodies bind the Thyroid hormone receptor causing activation of the receptor and increased thyroid hormone production.

Treatment: 

- Thionamides

- Radioactive Iodine Therapy

- Surgery

25

What are the mechanisms of Type II hypersensitivity? 

A image thumb
26

What is Type III Hypersensitivity

- Immune Complexes

- IgG mediated

- Antibody-antigen complexes if not removed deposit in tissues resulting in tissue damage by complement or phagocytes 

A image thumb
27

Explain the immune complexes formed in Type III hypersensitivity reactions

Immune complexes are formed due to:

- Infectious agents e.g. Streptococcal or Hepatitis B infection

- Environmental agents e.g. fungal spores, farmer's lung

- Autoantigens - e.g. DNA

 

- Normally removed by complement

- Constant activation of complement results in tissue damage 

A image thumb
28

Explain immune complex deposition

- Immune complexes are deposited in kidneys, blood vessels and synovial joints.

Presents as: 

- Vasculitis

- Glomerular Nephritis - Kidneys

- Arthiritis - Synovial Joints 

A image thumb
29

What is Systemic Lupus Erythamatosus 

- Autoantigen is DNA

- Failure of clearance of apoptotic cells

- Anti-DNA antibodies result in systemic damage to tissues - kidneys, skin, heart, joints

Treatment

Alklylating agents - e.g. cyclophoshamide suppress DNA synthesis

- Immunosupressants

- Biologic therapies - B cell depleting therapy Rituximab and an antibody which prevents B cell activation - Belimumab - both aim to reduce the amount of antibody in blood.

30

What is Arthus reaction? 

- Complication of vaccination e.g. tetanus if delivered in a bolus (intradermal vs intramuscular administration)

A image thumb
31

What is Serum Sickness? 

- Non-blanchable, painful purpuric patches

- Response to anti-venom to treat snake bite

- Anti-venom - polyvalent haemorrhagic

- IC formation in response to injection of foreign protein or serum 

32

Explain Type IV Hypersensivitiy 

- not AB mediated but cellular mediated

- Characterised by Th1 immune response

- Present as allergic reaction, but delayed - removal of a trigger, symptoms alleviated.

- Is an autoimmune disease - autoantigen exposure results in chronic disease 

A image thumb
33

Explain what Haptens are

- Haptens are small components of sensitising agents which are capable of inducing an immune response

- These can cross the epidermis of the skin and bind to self-protein to create neo-antigens

- Presentation of hapten by an APC results in the development of a memory response 

A image thumb
34

What is the DTH response

- Hapten-loaded APC present Ag to memory CD4 T cells.

- Activated T cells produce IFN-y which modulates keratinocytes function to become pro-inflammatory.

- Pro-inflammatory environment causes recruitment of T cells and macrophages

- T cells and macrophages play a role in resolution of inflammation. 

A image thumb
35

Explain the stages of the DTH response

- Primary exposure - sensitisation 

- DC induce memory cell production - Th1 type cells

Secondary Exposure - delayed type hypersensitivity response

Memory Th1 cells become activated to produce...

1) IFN-y and TNF-alpha - tissue destruction and inflammation

2) IL-2 to activate T helper and T cytotoxic cells

3) Chemokines for cell recruitment especially macrophages

- IL-3 and GM-CSF: production of monocytes and macrophages

 

36

Explain MS

A image thumb
37

What is RA? 

A image thumb
38

What is T cell mediated disease? 

A image thumb
39

What is contact sensitisation? 

Delayed Response - cells must migrate to the area

Compounds Include: nickel, poison oak/ivy, detergents

Treatment: trigger/avoidance

40

What is the Tuberculin Test? 

- Clinically important test to detect infection with Mycobacterium Tuberculosis 

A image thumb
41

What environmental/genetic factors affect autoimmune disease? 

Genetic Factors: MHC Class II

Environmental Factors: incidence varies throughout the world etc, smoking etc