Flashcards in Immunology Deck (116):
What is vaccination?
Deliberate administration of antigens to produce immunological memory
When are long lived T and B cells generated?
Adaptive immune response
Where do long lived plasma cells reside?
In immunological memory, how does IgG clear infection before symptoms occur?
Direct neutralisation of bacteria
Rapid mobilisation of phagocytes and complement
IgA blocks bacterial binding to mucous membranes
What are naïve B and T cells?
Mature but not yet activated (induce a strong response in 14-21 days)
What can naïve B and T cells become?
Effector or memory cells
What have memory B cells already undergone?
Ig class switching and hypermutation
What is immunisation?
The process through which an individual develops immunological memory to a disease
What is active immunisation?
Protection by the persons own immune system- usually permanent
What is passive immunisation?
Protection transferred by another person or animal- temporary
What are the two types of active vaccination?
Live attenuated vaccines or inactive vaccines e.g. killed, subunit or toxoid
What are some features of inactivated vaccines?
Do not multiply, not as effective, antibody based (not T cell), will diminish with time, multiple doses
What can under-inactivation cause?
Pathogens or toxins within the body
What can over-activation cause?
Ruins conformation of the antigen so there can be no antibody binding
What are some features of a live attenuated vaccine?
Similar to natural infection, organism must replicate, needs 1 dose
What is the advantage of inactivated vaccines over live attenuated ones?
Generally safer and easier to store
What is the most common example of natural passive immunisation?
Through transfer of maternal antibodies in placenta and maternal antibodies through breast milk
What antibody is transferred across the placenta?
What are examples of therapeutic passive immunisation?
Human immunoglobulin or monoclonal antibodies
What makes some organisms difficult to create vaccinations for?
Chronic/latent disease or rapidly evolving infections
What are some new approach vaccinations?
Mucosal vaccines, intranasal vaccine and preventative vaccines against cancer causing viruses
What is primary immunodeficiency?
Inherited abnormalities associated with a failure of development of components of the immune system
What are the hallmarks of immunodeficiency?
Serious, persistent, unusual, recurrent infections
What is classed as recurrent infection?
2 major or 1 major and recurrent minor infections in one year
What are typical features of immunodeficiency in general?
Weight loss, failure to thrive, severe skin rash, chronic diarrhoea, mouth ulcers, autoimmune disease, family history
What is more common, primary or secondary immunodeficiency?
What are causes of secondary immunodeficiency?
Physiological, infections, treatment, malignancy, nutritional disorders
What do defects of phagocyte production usually cause?
Failure to produce neutrophils or a failure of their maturation
What is Kostmann Syndrome?
Rare autosomal recessive disorder of severe chronic neutropenia
What are signs of Kostmann Syndrome?
Infections after birth, fever, irritability, ulcers, failure to thrive
What is the supportive treatment for Kostmann Syndrome?
Prophylactic antibiotics and antifungals
What is the definitive treatment for Kostmann Syndrome?
Stem cell transplant, granulocyte colony stimulating factor
What is leukocyte adhesion deficiency?
Genetic defect in leukocyte integrins to cause a failure of neutrophil adhesion and migration
What does leukocyte adhesion deficiency show?
Leukocytosis (high WCC) and localised bacterial infections
What are opsonins?
Binding enhancers for phagocytosis
What do opsonin defects cause?
Defective phagocytosis but not significant disease
In general, how are phagocyte deficiencies treated?
Oral/IV antibiotics, surgical drainage of abscess, bone marrow transplant
What is chronic granulomatous disease?
Failure of oxidative killing mechanisms. It is x-linked deficiency of NADPH oxidase
What does CGD result in?
Excessive inflammation and granuloma formation, recurrent deep bacterial and fungal infections, failure to thrive, lymphadenopathy, hepatosplenomegaly
What is the prophylactic treatment for CGD?
Prophylactic antibiotics and antifungals
What is the definitive treatment for CGD?
Stem cell transplant, gene therapy
What are organisms which can hide from the immune system in cells?
Salmonella, chlamydia, rickettsia
Where is it common for organisms to hide in the body?
What is reticular dysgenesis?
Failure to produce neutrophils, lymphocytes, monocytes/macrophages, platelets
How is reticular dysgenesis treated?
Only by stem cell transplant
What is SCID?
Failure to produce lymphocytes in the thymus
When are signs of SCID?
Unwell by 3 months, persistent diarrhoea, failure to thrive, infections of all types, family history
What is the commonest form of SCID?
X-linked mutation in the IL2 receptor which results in the inability to produce cytokines
What is the clinical presentation of SCID?
Low/absent T cells, normal/increased B cells, poorly developed lymphoid tissues
How is SCID treated?
Prophylactic antibiotics, stem cell transplant, gene therapy
What is DiGeorge syndrome?
Defect of the 3rd/4th pharyngeal pouch so there is failure of thymus development which results in T cell immunodeficiency
What are physical signs of DiGeorge syndrome?
Low set ears, high forehead, cleft palate, small mouth
What are clinical signs of DiGeorge syndrome?
Hypocalcaemia, T cell lymphopenia, congenital heart disease, recurrent bacterial and viral infections, frequent fungal infection
What is the treatment for DiGeorge syndrome?
Prophylactic antibodies and treatment of infection and immunoglobulin replacement
What is the good thing about DiGeorge syndrome?
T cell function improves with age
What do antibody deficiencies present as?
Recurrent bacterial infections
What is Bruton's X-linked Hypergammaglobulinaemia?
Failure to produce mature B cells
What is selective IgA deficiency?
A genetic component which only affects about 1/3rd of sufferers
What is CVID?
Lots of different diseases, low IgG/IgA/IgE
How does CVID present?
Recurrent bacterial infections associated with autoimmune disorder
What type of hypersensitivity reactions are allergic responses?
What is an allergic response?
IgE mediated antibody response to an external antigen
What antibodies do non-atopic episodes involve?
IgG and IgA
Allergen specific T cells are activated by allergen derived peptides in allergic reactions. What does this cause?
Differentiation of CD4+ T cells into effector Th2 cells which produce cytokines
Which interleukins does Th2 produce to synthesise IgE by B cells?
IL4, 13 and 5
What does the production of IgE during allergic responses result in?
Eosinophil and mast cell recruitment to the site of allergen
Abnormal response to allergens is the normal response to what?
Mast cells release preformed substances. What are these?
Histamine, heparin and tryptase
Mast cells synthesise molecules on demand. What are these?
Leukotrienes, prostaglandins and cytokines
What do mast cells express receptors for?
The Fc region of the IgE antibody
When do clinical features of allergic responses occur?
What are clinical features of allergic responses?
Urticaria, angioedema, asthma, allergic rhinitis, conjunctivitis and anaphylaxis
In extrinsic asthma, what does the release of histamine and other inflammatory mediators result in?
Muscle spasm (bronchodilation and wheeze), mucosal inflammation and inflammatory cell infiltrate (secretions)
What do non-allergic responses occur as a result of?
Spontaneous mast cell degranulation
What can non-allergic responses occur as a result of?
Drugs, thyroid disease, idiopathic, physical urticaria
What is the management of type 1 hypersensitivity reactions?
Allergen avoidance, block/prevent mast cell activation, anti-inflammatory agents, management of anaphylaxis, immunotherapy
What drugs block mast cell activation?
What drugs prevent mast cell activation?
Antihistamines, leukotriene receptor antagonists
What are anti-inflammatory agents?
What is given to manage anaphylaxis?
What do type II hypersensitivity reactions involve?
Direct cell killing
What are type II hypersensitivity reactions triggered by?
Antibody binding to an antigen on the cell surface or extracellular matrix
What is the result of type II hypersensitivity reactions?
Cell lysis or inflammatory reactions at the site of antibody deposition
When the antibody binds to a cell surface antigen, what does this result in?
Activation of complement for cell lysis and opsonisation
What antibodies are involved in type II hypersensitivity reactions and why?
IgG and IgM as they activate complement
Complement activation results in the activation of C3. What does this cause?
Chemotaxis, solubilisation of immune complexes, direct killing of bacteria and opsonisation
What type of bacteria does complement generally kill and how?
Directly encapsulated bacteria through the membrane attack complex
What complement proteins are involved in type II hypersensitivity reactions?
C3a and C5a
How does direct cell killing take place in type II hypersensitivity reactions?
Through B cells producing antibodies directed against the cell membrane protein
What other immune system components are involved in type II hypersensitivity reactions?
Eosinophils and natural killer cells
What are clinical examples of type II hypersensitivity reactions?
Blood cells (transfusion reactions), Goodpasture's syndrome, myasthenia gravis, binding of antibodies to TSH receptor
How are type II hypersensitivity reactions managed?
Removal of the pathogenic antibody (blood removed by cell separator) or immunosuppression
What are type III hypersensitivity reactions?
Immune complex mediated
What is the key feature of type III hypersensitivity reactions?
Antibodies binding to soluble antigens
What triggers type III reactions and what happens to these?
Excess antigens- antibody binds to them to form small immune complexes
Where are the immune complexes of type III reactions found?
Trapped in blood vessels, joints and glomeruli
What is activated in type III reactions?
What is the result of type III reactions?
Antibody mediated phagocytosis and infiltration and activation of neutrophils and macrophages to result in tissue damage
A clinical example of type III reactions is farmer's lung. What happens here?
Inhaled fungal particles are deposited which stimulates antibody binding
What does immune complexes in the walls of the alveoli and bronchioles result in?
Leukocyte accumulation and activation
What are symptoms of leukocyte accumulation in the lungs?
Wheezing and malaise 4-8 hours after antigen exposure. Can also be dyspnoea, pyrexia and a dry cough
What are other examples of type III hypersensitivity reactions?
Acute hypersensitivity pneumonitis, systemic lupus erythematosus
What is the difference between types II and III reactions?
Type II is localised and type III is systemic
How do you test for type III reactions?
Test for specific IgG antibodies
How do you manage type III reactions?
Allergen avoidance, steroids, immunosuppression
What are type IV reactions?
What are autoimmune examples of type IV reactions?
Type 1 diabetes, psoriasis, rheumatoid arthritis
What are non-autoimmune examples of type IV reactions?
Nickel hypersensitivity, TB, leprosy, sarcoidosis, cellular rejection of organ transplant
What differentiates type IV reactions?
T cell mediated
In type IV hypersensitivity reactions, what is generated on initial sensation to an antigen?
Effector Th1 cells
What happens on subsequent exposure to antigens in type IV reactions?
Activation of Th1 cells, recruitment of macrophages, lymphocytes and neutrophils to cause persistent inflammation
What do Th1 cells activate in type IV reactions?
Interferon gamma cytokines
What is poison ivy an example of?
Type IV reaction
What is sarcoidosis?
Multi-system granulomatous disease
What type of immune response is involved in sarcoidosis?
Non specific response involving T cells and macrophages