Theme 3: Inflammation, Infection and Immunology: Part 3 Flashcards
1
Q
What are the key features of the innate immune system?
A
- pre-programmed
- no memory
- triggered within seconds
2
Q
What are the key features of the adaptive immune system?
A
- highly tailored to infection
- memory
- takes 4-6 weeks
3
Q
Which cells of the innate immune system are APCs that recognise threat?
A
- dendritic cells
- macrophages/monocytes
4
Q
Which cells of the innate immune system engulf and destroy threat?
A
- phagocytes (macrophages, neutrophils)
- granulocytes (neutrophils, eosinophils, mast cells, basophils)
5
Q
What are cytokines?
A
- proteins of the innate system
- chemical signals which modulate cell activity or attract cells (chemokine_
6
Q
What are complement proteins?
A
- proteins of innate system
- multiple functions: opsonisation, killing, activation, chemoattraction
7
Q
What are the functions of lymphocytes?
A
- B lymphocytes - secrete antibodies: humoral immunity
- Cytotoxic T lymphocytes: kill / cellular immunity
- Helper T lymphocytes: secrete growth factors (cytokines) which control immune response
- Suppressor T lymphocytes - dampen down immune response
8
Q
What is autoimmunity/ auto inflammation?
A
innappropriately increased response to danger signals
9
Q
What is immunodeficiency?
A
inappropriately decreased response to danger signals
10
Q
Which factors pre-dispose to autoimmune conditions?
A
- sex (hormonal influence) - women more than men
- age - more common in elderly
- environmental triggers - infection, smoking
11
Q
Which cells cause autoimmunity?
A
- autoreactive B cells and autoantibodies
- directly cytotoxic, activation of complement
- autoreactive T cells
- directly cytotoxic, cytokine production
12
Q
What is Hashimoto’s thyroiditis?
A
- destruction of thyroid follicles by autoimmune processes
- associated with autoantibodies to thyroglobulin and thyroid peroxidase
- leads to hypothyroidism
- symptoms: weight gain, fatigue, cold, hair loss, constipation
13
Q
What is graves disease?
A
- innappropriate stimulation of thyroid gland by anti-TSH-autoantibody
- leads to hyperthyroidism
- symptoms: weight loss, anxiety, diarrhoea, palpitations, hot, goitre
14
Q
What are examples of systemic autoimmune diseases?
A
- systemic lupus erythematosus (SLE)
- scleroderma
- polymyositis
- vasculitis
15
Q
What is urticaria?
A
skin rash
16
Q
What is neutrophilic urticarial dermatosis?
A
- neutrophillic dermal infiltrate with substantial interstitial spreading
- absence of confluence of neutrophils
- no oedema
17
Q
What are 3 NLRP3-related autoinflammatory diseases?
A
- Familial cold urticaria
- relatively mild
- autosomal dominant
- cold induced rash
- arthralgia (pain at joints)
- conjunctivitis - Muckle Wells syndrome
- autosomal dominant
- moderate severity
- urticarial rash
- sensorineural deafness
- AA amyloidosis (25%) - NOMID/CINCA
- sporadic
- severe
- progressive chronic meningitis
- deafness, visual and intellectual damage
- destructive arthritis
18
Q
What are the differences between auto inflammation and autoimmunity in terms of:
- Immune response
- Main cellular involvement
- Antibody involvement
- Clinical features
- Therapy
- Example diseases
A
- autoinflammation - innate immunity
autoimmunity - adaptive immunity - autoinflammation - neutrophils, macrophages
autoimmunity - B and T cells - Autoinflammation - few or no autoantibodies
autoimmunity - autoantibodies present - autoinflammation - recurrent, unprovoked attacks
autoimmunity - continuous progression - autoinflammation - anti-cytokine (IL-1, TNF)
autoimmunity - anti-B and T cell - autoinflammation - chrons disease
autoimmunity - monogeny ALPS and IPEX
19
Q
What is immunosuppression?
A
a natural or artificial process which turns off the immune response, partially or fully, accidentally or on purpose
20
Q
What are examples of secondary or acquired immunodeficiencies?
A
- stress
- surgery/burns
- malnutrition
- cancer
- irridiation
- AIDS
21
Q
What is primary immunodeficiency?
A
- very rare
- often in childhood but can present in adult life
- recurrent, unusual and opportunistic infection
22
Q
Why are defects in T cells more severe than defects in B cells?
A
B cells also need T cell help
23
Q
What would happen if you have defects in both B and T cells?
A
- severe combined immunodeficiency syndromes (SCID)
- bone marrow transplant is curative
- gene therapy
24
Q
What is hypersensitivity?
A
- a reaction produced by the normal immune system in a pre-sensitised (immune) host
- undesirable, damaging, uncomfortable, sometimes fatal
25
What did Coombs and Gell (1963) discover?
IV types of hypersensitivity - I, II, III, IV
26
Describe type 1 hypersensitivity
- IgE antibody binds to mast cell and causes degranulation of mast cell
- fast onset, can be mild, moderate or severe
- primary response: histamine, proteases, chemotactic factors
- late phase response: eosinophils, central role for Th2 T cell
27
What are the systemic effects of histamine?
- blood clots
- gastric acid secretion
- vasodilation
- bronchoconstriction
- increases the permeability of the capillaries
- adrenaline is released
- swelling and inflammation
- infrequent heart beat - tachycardia, bradycardia
28
What is anaphylaxis?
an acute, potentially life-threatening IgE mediated systemic hypersensitivity reaction
29
What are the symptoms of mild type 1 hypersensitivity?
- itchy eyes or nose
- cutaneous pruritus - itching of the skin
- urticaria - red rash
- oral tingling
- abdo pain/ nausea/ vomiting
- runny nose, sneezing
30
What are the symptoms of moderate-severe type 1 hypersensitivity?
- diffuse urticaria and angioedema
- severe abdominal pain, vomiting diarrhoea
- SOB
- cough, wheezing and cyanosis
- hypotension
- dizziness, loss of consciousness, respiratory arrest
31
What is the dual allergen exposure hypothesis?
- early cutaneous exposure to food protein through a disrupted skin barrier lead to allergic sensitisation
e. g excsma disrupts the skin barrier so can lead to allergies
- whereas early oral exposure to food allergens induces tolerance
32
Can allergies have a genetic influence?
- allergies caused by a combination of genetic and environmental factors
- however, genetic influences are not sufficient for disease, only susceptibility
33
What is the atopic triad
- eczma
- asthma
- rhinitis
34
How do we diagnose allergies?
- history
- specific IgE
- skin prick test
- intra-dermal test
- oral challenge test (gold standard)
35
What is a positive test for a skin prick test?
where there is a hive that is >2mm bigger than negative control
36
What is asthma?
- disease of inflammation and hyperactivity of the small airway
- immediate symptoms are IgE-mediated
- damage to airways due to late phase response
37
What is type II hypersensitivity?
- cytotoxic
- IgG/ IgM Ab response against combined self/foreign antigen at cell surface
- complement activation/phagocytosis/ ADCC
- onset minutes to hours
- cell lysis/ necrosis
38
what is a common antigen associated to type II hypersensitivity?
penicillin
39
give 2 diseases resulting in type II hypersensitivity
- goodpasture's nephritis
| - blood transfusion reaction
40
What is a blood transfusion reaction?
- example of type II hypersensitivity
- if incorrectly matched blood
- patients APC's detect the foreign antigen, present it to B cells which makes antibodies which activates complement and has cytotoxic action
- takes hours to a day
41
What is the MAC Protein complex?
- C1 binds IgG/M and the complement cascade follows
- C3 activation generating C3a + C3b
- focused target cell lysis
42
What is type III hypersensitivity?
- immune complex deposition
| - IgG/ IgM Ab against soluble antigen
43
What are the clinical features of type III hypersensitivity?
- onset 3-8hrs
- vasculitis
- traditional cause: serum sickness
- associated diseases - SLE
44
What is the difference between type II and type III hypersensitivity?
- same antibodies but bind to different things
- type II sensitivity - IgG binds to cell
- type III sensitivity - antibody binds to soluble antigen
45
What is an example of Type III hypersensitivity condition?
Systemic lupus erythematosus (SLE)
| -B cells recognises self as foreign so autoimmunity results
46
Explain the complement cascade in Type III hypersensitivity ?
- C1 from the complement system binds the antibody and C1-9 follow with increased permeability of vessels - triggers complement pathway
- C3/4 used in large amounts - key blood test - as complement is used up
47
What is type IV hypersensitivity?
- delayed onset: 48-72hrs
- antigen specific T-cell mediated cytotoxicity
- erythema (redness of skin)
- common antigens: metals e.g nickel, poison ivy
- associated diseases: contact dermatitis
48
Name 3 chemical mediators produced by a mast cell?
leukotrienes, histamine, prostaglandins
49
What is anaphylaxis?
Massive degranulation of mast cells causing the release of chemical mediators
50
What is perioperative anaphylaxis?
occurs during the period of anaesthesia and surgery
51
How do we treat anaphylaxis?
- first, adrenaline and fluids
- fluids are needed because with increased vascular permeability that histamine causes you get a leakage of fluid from the intravascular compartments
- if this doesn't work, consider vasopressin and glucagon
- steroids, antihistamines
52
What are the two functions of adrenaline?
1. treats symptoms - increase systemic vascular tone
| 2. stops anaphylaxis - stops mast cell degranulation
53
Why do we collect tryptase samples instead of histamine in a allergic reaction?
- tryptase is one of the chemical mediators released from mast cells when they degranulate
- histamine has a very short half life so we cannot capture the histamine peak during anaphylaxis
54
What are the main causal agents for preoperative anaphylaxis?
- antibiotics
- neuromuscular blocking agents
- chlorhexidine
- teicoplanin is most allergenic anaesthetic drug
55
What is a challenge test?
give allergenic e.g penicillin in controlled environment and watch closely for symptoms
