Immunology Flashcards
List causes of secondary immune deficiency
Physiological (age, prematurity) Infection (HIV, measles) Treatments (immunosuppressants, chemo, CCS) Malignancy (haematological, mets) Biochemical (malnutrition, RF, DM)
What is a granuloma?
An organised collection of activated macrophages and lymphocytes triggered by antigens or inert foreign materials
List differential diagnosis of lung granuloma
Sarcoidosis Mycobacterial disease e.g. TB, leprosy Berylliosis, silicosis and other dust diseases Chronic hypersensitivity pneumonitis Foreign bodies
How do antibody deficiencies commonly present?
Recurrent bacterial infections (typically RT or GI)
Antibody-mediated AI diseases (thrombocytopaenia, AI haemolytic anaemia)
State two common primary antibody deficiencies
Common variable immune deficiency (IgG, IgM, IgA)
Selective IgA deficiency
State two secondary causes of recurrent bacterial infections and hypogammaglobulinaemia
Protein loss (nephrotic syndrome) Failure of protein synthesis (CLL, myeloma, NHL)
What are the three types of complement pathways activated by an antigen on the microbial surface?
Alternative pathway
Lectin pathway
Classical pathway
Describe the alternative complement pathway
Activated when C3b protein binds to a microbe and triggers the formation of C5, C5b –> 9 and then cell lysis
Describe the lectin complement pathway
Starts with MBL protein and when activated triggers a cascade of C4 and C2 protein (C3 convertase) eventually causing lysis
Describe the classical complement pathway
Initiated by IgG and IgM complexes and when activated triggers a cascade of C4 and C2 protein (C3 convertase) eventually causing lysis
List functions of complement
Opsonization (better eating of bugs by phagocytes)
Lysis (direct killing by punching cells)
Chemotaxis (calling in troops)
What is the consequence of complement deficiency?
Predisposes to bacterial infection especially meningitis
What are NK cells?
Kill cells that lack MHC molecules on surface (including cancer cells) and have no long term memory - part of innate immunity
What is the consequence of NK cell defects?
Predispose to recurrent VZV, HSV, CMV, HPV NK cells
What are toll-like receptors?
Expressed on phagocytes and dendrites and act as burglar alarms for microbes by responding to PAMPs, causing the release of cytokines
TLR dysfunction can lead too..
Immunodeficiency (too little)
Autoimmunity (too much)
What do TNF inhibitors block?
Pro-inflammatory cytokines e.g. TNF alpha preventing granuloma formation
What is the mechanism behind biologic drugs?
Artificial antibodies that block the body’s own proteins (TNF) so they act like passive immunisation
List the types of transplant rejection and the time at which they occur
Hyperacute rejection (minutes to hours)
Acute cellular rejection (5-30 days)
Acute vascular rejection (5-30 days)
Chronic allograft failure (>30 days)
Vaccination produces memory in B cells. What is meant by this?
Long-lived memory B cells are generate during the primary immune response that survive after the antigen has been eliminated
These can reactivate in response to a second encounter with that specific antigen producing IgG quickly
Vaccination produces memory in T cells. What is meant by this?
Vaccination stimulates rare T cells and induces a strong T cell response
Some become effector cells which either die by apoptosis after antigen has gone or become memory cells
Which antibody is produced first in a primary infection?
Immediate IgM response
IgG produced later
Which antibodies are produced in secondary infection?
IgG antibody response is greater and more prolonged
List advantages of inactivated vaccines
Elicit good antibody responses
Usually safe
List disadvantages of inactivated vaccines
Killed organisms don’t stimulate a good response
Requires multiple injections as no clonal expansion
What is meant by a whole cell inactivated vaccine? Give an example
Whole organism used
Polio (or ‘6 in 1’)
What is meant by a fractional inactivated vaccine? Give some examples
Only part of the organism used in the vaccine
Subunit (Hepatitis B)
Toxoid (Diphtheria, tetanus)
Pure polysaccharide (HIB)
List advantages of activated vaccines
All relevant effector mechanisms elicited
Localised strong response
Usually only one dose
List disadvantages of inactivated vaccines
May not be safe (can cause virulence, infection in immunocomprimised)
Fragile (stored carefully)
Give an example of a viral live attenuated vaccine
Measles
Mumps
Rubella
Give an example of a bacterial live attenuated vaccine
BCG
Measurement of which antibody is likely to aid diagnosis of SLE?
Anti-ds DNA
Measurement of which antibody is likely to aid diagnosis of coeliac disease?
Anti-TTG igA antibody
Measurement of which antibody is likely to aid diagnosis of myasthenia gravis?
Anti-AchR antibody
Measurement of which antibody is likely to aid diagnosis of Sjogren’s syndrome?
Anti-Ro
Measurement of which antibody is likely to aid diagnosis of rheumatoid arthritis?
Anti-cyclic citrullinated protein (CCP)
Measurement of which antibody is likely to aid diagnosis of polymyositis?
Anti-Jo-1
Measurement of which antibody is likely to aid diagnosis of systemic sclerosis?
Diffuse: anti-Scl-70
Limited: anti-centromere antibody
In what situations would biologics be used as first line over other immunosuppressants?
Liver cirrhosis/renal failure
TB risk
What are the features of primary immunodeficiency?
Adult onset
History of opportunistic infections
State the main clinical side effect of methotrexate
Hepatotoxicity
