Immunology Flashcards
Hallmark of immune deficiencies
SPUR -
S - serious infections (unresponsive to oral antibiotics)
P - persistent infections (early structural damage, chronic infections)
U - unusual infections (unusual organisms or sites)
R - recurrent infections (2 minor or 1 major a year)
Other features of immune deficiency
Weight loss or failure to thrive Severe skin rash (eczema)? Chronic diarrhoea Mouth ulcers Unusual autoimmune disease Family history
2 classifications of immunodeficiencies
Primary (rare)
Secondary (common)
2 branches of the immune system
Innate
Acquired
Cells in the innate immune system
Macrophages
Neutrophils
Mast cells
NK cells
Proteins of innate immune system
Complement
Acute phase protein
Cytokines
Function of innate immune system
Rapid clearance of microorganisms
Stimulates acquired immune response
Buys time for acquired immune response
Cells in the acquired immune system
B lymphocytes
T lymphocytes
Proteins in the acquired immune system
Antibody
Function of acquired immune system
Adaptive response after exposure to antigen
Responsive to unlimited number of molecules
Immunological memory
Examples of phagocytes
Neutrophils
Monocytes/Macrophages
Functions of phagocytes
Initiation and amplification of inflammatory response
Scavenge for cellular and infectious debris
Produce inflammatory molecules which regulate other parts of IS
Resolution and repair
Clinical features of phagocytes deficiencies
Recurrent infections
May affect common or unusual sites
All types of bacteria and fungi
Where are phagocytes found
Bone marrow or within tissues
What is Kastmann syndrome?
Rare autosomal recessive disorder
Severe chronic neutropenia
Clinical presentation of Kastmann syndrome
Infections (0 - 2 weeks old) Fever Irritability Oral ulcers Failure to thrive
Treatment of Kastmanns syndrome
Supportive - prophylaxis antibiotics & antifungals Definitive - stem cell transplant G-CSF
What is leukocyte adhesion deficiency?
Rare primary immunodeficiency
Caused by genetic defect
Results in failure of neutrophil adhesions and migration
Clinical features of leukocyte adhesion deficiency
Marked leukocytos
Localised infections - difficult to detect
What causes chronic granulomatous disease?
Failure of oxidative killing mechanisms
What are the features of chronic granulomatous disease?
Recurrent deep bacterial infections Recurrent fungal infections Failure to thrive Lymphadenopathy & hepatosplenomegaly Granuloma formation
Investigation for chronic granulomatous disease
NBT test
Treatment of chronic granulomatous disease
Supportive - prophylactic antibiotics/anti-fungals Definitive - stem cell,transplant - gene therapy
Why are intracellular organisms difficult for the immune system?
Hide from immune system by locating within cells
Can hide in immune cells (esp. macrophages)
Need specific strategies to clear infection
Examples of intracellular organisms
Salmonella
Chlamydia
Rickettsia
What network defends against intracellular organisms?
IL12- gIFN network
Brief summary of IL12-gIFN network
Infected macrophages stimulated to produce Il12
IL12 induces T cells to produce gIFN
gIFN feeds back to macrophage and neutrophils
Stimulate TNF production
Activate NADPH
Stimulates oxidative pathways
Causes of defects in IL12-gIFN network
Single gene defects
- gIFN receptor deficiency
- IL12 deficiency
- IL12 receptor deficiency
Treatment of phagocyte deficiencies
Supportive - prophylaxis - oral/IV antibiotics - surgical drain of abscess Definitive - bone marrow transplant - gIFN therapy - gene therapy
4 organisms that the immune system tackles
Viruses (e.g. Influenza)
Bacteria (e.g. Staph/Strep)
Protozoa (e.g. Amoeba)
Worms (e.g. Guinea worm)
Where do lymphocytes mature?
Thymus gland
Where is the thymus gland?
Just in front of the heart in the mediastinum
How is lymph returned to the systemic circulation?
Thoracic duct
What does the thoracic duct join with?
Left subclavian vein
What does IL-1 do?
Causes fever and activates lymphocytes
What does Il- 6 do?
Causes fever, stimulates the liver to produce acute phase proteins such as CRP, activates lymphocytes and promotors antibody production
What does IL-8 do?
Causes neutrophil Chemotaxis
What does IL-12 do?
Activates NK cells and TH1 cells (important for intracellular infections)
What does TNF-alpha do?
Increases vascular permeability to allow immune cells to reach tissues
What do IL-4, IL-5 and IL-13 do?m
Promote IgE production and eosinophilic reactions inpatients with allergies
What does gamma interferon do?
Activates cell mediated immunity in viral infections
What does IL-10 do?
Has an anti inflammatory affect
What do co stimulators molecules do?
Encourage activation of the adaptive immune system
How are dendritic cells involved in antigen presentation?
Carry digested antigens to lymph nodes
Present to TH0 cells with MHC II complexes
What can TH0 cells differentiate into?
TH1 and TH2
How are hypersensitivity reactions classed?
Type I: immediate hypersensitivity
Type II: direct cell killing
Type III: Immune complex mediated
Type IV: delayed type hypersensitivity
Summary of the path ophthalmology of allergic reactions
Production of specific IgE directed against antigen
IgE allergen complex binds to mast cells via Fc receptors
De granulation of mast cells
Release of preformed and newly synthesised inflammatory molecules (e.g. histamine, leukotrienes)
What is sodium cromoglycate?
Mast cell stabiliser
Mechanism of action of anti-histamines
H1 receptor antagonists
Block affects of histamines
Example of leukotriene receptor antagonist
Montelukast
Action of adrenalin in anaphylaxis
Acts on B2 adrenergic receptors to constrict arterial smooth muscle
Increases blood pressure limiting vascular leakage
Dilates bronchial smooth muscle
Key feature of Type II hypersitivity reaction
Antibody binds to cell surface antigen
4 actions of complement
Chemotaxis (recruits neutrophils and macrophages)
Solubilisation (of immune complexes)
Direct killing (of encapsulated bacteria - MAC punches hole)
Opsonisation (tomato ketchup)
Clinical example of type II hypersensitivity reaction
Blood donor rejection
What is plasmapheresis?
Cell separator to remove pathogenic antibody
Example of type III hypersensitivity reaction
Farmers lung
Pigeon fanciers lung
Systemic lupus erythematosus (SLE)
Examples of type IV hypersensitivity
Nickel hypersensitivity
Management of sarcoidosis
NSAIDS (for acute onset)
Systemic corticosteroids
- block T cell activation
- block macrophage activation
Diseases characterised by type IV hypersensitivity and granuloma formation
Sarcoidosis
Tuberculosis
Leprosy (some forms)
Berylliosis, silicosis and other dust diseases
Chronic stage of hypersensitivity pneumonitisis
Types of transplant rejection
Hyperacute rejection
Acute cellular rejection
Acute vascular rejection
Chronic allograft failure
Treatment for transplant rejection
Immunosuppressive
