Immunology Flashcards
What are some causes of secondary immune deficiency?
- Infections - HIV, measles
- Drugs - immunosuppressants, anti-cancer drugs, corticosteroids
- Malignancy - lymphoma, leukaemia, myeloma, metastasis
- Biochemical and nutritional disorders - malnutrition, T1DM, T2DM, renal insufficiency/dialysis
What is a granuloma?
An organised collection of activated macrophages and lymphocytes
What is the underlying pathology/immunology of a granuloma?
- Non-specific inflammatory response
- Results in activation of T lymphocytes and macrophages
- Failure of removal of the stimulus results in persistent production of activated cytokines
- End result is organised collection of persistently activated cells
What are some of the differential diagnoses for a lung granuloma?
Sarcoidosis, TB, leprosy, silicosis, chronic stage of hypersensitivity pneumonitis, foreign bodies
How can antibody deficiencies present?
- Recurrent bacterial infections e.g. recurrent URTI and LRTI
- Antibody mediated autoimmune diseases e.g. thrombocytopenia, autoimmune haemolytic anaemia
Common variable immune deficiency (CVID) is a primary antibody deficiency, what are the features of CVID?
- Low IgG, IgA and IgM
- Recurrent bacterial infections esp respiratory
- Often associated with autoimmune disease
What is another example of a common primary antibody deficiency?
- Selective IgA deficiency
- 2/3rds are symptomatic
- 1/3rd have recurrent RT infections
What are some secondary causes of recurrent bacterial infections and hypogammaglobulinaemia?
- Protein loss - nephrotic syndrome
- Failure of protein synthesis - lymphoproliferative disease e.g. CLL
In basic terms, what is complement?
Protein constantly secreted by the liver to act as a sticky coat for intruders in order to turbo-boost immediate immune defence
What does complement deficiency result in?
Predisposes to bacterial infection especially meningitis
What is the function of natural killer cells?
- Kill cells that lack MHC
- Natural means that they have no need for antigen specificity
- No long term memory
- NK cells are an innate immunity feature that eliminate cancer cells
What can NK cell defects result in?
Predispose to recurrent VZV, HSV, CMV, HPV
What receptors are involved in innate recognition of invaders and what do these respond to?
- Toll like receptors are expressed on phagocytes and dendrities as built in burglar alarm for microbes
- Respond to PAMPs (pathogen-associated molecular patterns)
What happens as a result of TLR activation?
Pro-inflammatory cytokines and type 1 interferon secretion
What can TLR dysfunction cause and what can be used to remedy this?
- Dysfunction can lead to immunodeficiency (too little) or autoimmunity (too much)
- TLR-activators are used to boost immunity (anti-skin cancer creams e.g. imiquimod)
What do TNF inhibitors do?
- Block pro-inflammatory cytokines
- These drugs are foreign proteins so the immune system can form antibodies against them
How do most biologic drugs work and what are some examples?
- Most are artificial antibodies that block the body’s own proteins so they act just like passive immunisation and have to be injected every couple of weeks
- Since they are normal proteins, their metabolism is not dependent on liver or renal function
- Adalimumab = anti-TNF
- Pembrolizumab = anti-PD1
- Secukinumab = anti-interleukin 17
Name the types of transplant rejection
- Hyperacute rejection minutes-hours
- Acute cellular rejection 5-30 days
- Acute vascular rejection 5-30 days
- Chronic allograft failure >30 days
What is the pathology and mechanism behind hyperacute rejection?
- Thrombosis and necrosis, type II hypersensitivity
- Preformed antibody and complement fixation
What is the pathology and mechanism behind acute cellular rejection?
- Cellular infiltration, type IV hypersensitivity
- CD4 and CD8 T cells
What is the pathology and mechanism behind acute vascular rejection?
- Vasculitis, type II hypersensitivity
- De novo antibody and complement fixation
What is the pathology and mechanism behind chronic allograft rejection?
- Fibrosis and scarring
- Immune and non-immune mechanisms
What do memory B cells do and how do they form?
- They are generated during primary immune responses and can survive for many years even after the antigen has been eliminated
- Memory B cells rapidly re-activate in response to a second encounter with that specific antigen
Vaccination stimulates rare naive T cells, what happens as a result of this?
- Induces a strong T cell response in 14-21 days
- Some become effector T cells which mostly die by apoptosis but some become memory T cells
What are some of the advantages of inactivated vaccines?
- Quick/easy
- Can be made quickly (prevent epidemics)
- Elicit good antibody responses
- Easy to store
- Usually safe
What are some of the disadvantages of inactivated vaccines?
- Not very potent
- Many killed organisms don’t stimulate good immune response because they don’t replicate or disseminate
- Doesn’t stimulate clonal expansion of B and T cells, thereby requiring multiple injections
What are some examples of inactivated vaccines?
- Whole cell vaccines e.g. polio, hep A, rabies
- Fractional vaccines;
- subunit vaccines e.g. hep B, pertussis
- toxoid e.g. diphtheria, tetanus
- pure polysaccharide vaccines e.g. haemophilus influenzae type B
What diseases are included in the 6-in-1 vaccine?
- Polio
- Hep B
- Pertussis
- Diphtheria
- Tetanus
- Haemophilus influenzae type B
What are some of the advantages of live attenuated vaccines?
- All relevant effector mechanisms elicited
- Localised, strong response
- Usually only one single dose required
What are some of the disadvantages of live attenuated vaccines?
- Safety - may revert to virulence, may cause infection in immune-compromised host
- Fragile - must be stored and handled carefully
Name some examples of live attenuated vaccines
- Viruses - measles, mumps, rubella, chickenpox, yellow fever, rotavirus, small pox
- Bacterial - BCG, oral typhoid
