immunology Flashcards
what is a granuloma?
an organised collection of activated macrophage + lymphocytes
- non-specific inflammatory response triggered by diverse antigenic agents or by inert foreign materials
- results in activation of T lymphocytes + macrophages
- failure of removal of the stimulus results in persistent production of activated cytokines
–> end result = organised collection of persistently activated cells
ifferential diagnosis of lung granuloma
sarcoidosis
myobacterial disease - Tb, leprosy
silicosis + other dust diseases
chronic stage of hypersensitivity pneumonitis
foreign bodies
presentation of antibody deficiencies
recurrent bacterial infections - resp, GI (viral less common)
antibody mediated autoimmune diseases
- idiopathic thrombocytopenia
- autoimmune haemolytic anaemia
common primary antibody deficiencies
common variable immune deficiency (CVID)
selective IgA deficiency
common variable immune deficiency (CVID)
low IgG, IgA + IgM
- causes most unknown
recurrent bacterial infections - esp resp
often assoc with autoimmune disease
selective IgA deficiency
VERY COMMON!!
2/3rd individuals asymptomatic *
other1/3rd -> recurrent resp infections
genetic component, but cause unknown
differential diagnosis of recurrent bacterial infections + hypogammaglobulinaemia
primary = antibody deficiency
secondary
- protein loss - nephrotic syndrome, protein losing enteropathy
- failure of protein synthesis - lymphoproliferative disorder (CLL, myeloma, NHL)
natural killer cells
innate-immunity feature to eliminate cancer cells
lack MHC molecules on surface
“natural” -> no need for antigen specificity
no long term memory
natural killer cell defects
predisposes to recurrent VZV, HSV, CMV, HPV NK cells
innate recognition of invaders
“toll- like receptors” (TLRs)
- respond to “PAMPS” (pathogen-assoc molecular patterns)
-> expressed on phagocytes + dendrites as built in burglar alarm for microbes - activation triggers proinflammatory cytokines + type 1 interferon secretion
what can TLR dysfunction cause?
(toll-like receptors -> built in burglar alarm)
can lead to immunodeficiency (too little) or autoimmunity (too much)
TLR activators use?
(toll-like receptors -> built in burglar alarm)
are used to boost immunity (“anti-skin cancer creams”) - imiquimoid
TNF-alpha
block pro-inflammatory cytokines
TNF-alpha is an immediate-early “fire alarm” signal in response to many stressors (microbes, stress, chemicals)
“biologic” drugs
MOST are artificial antibodies that block the bodys own proteins - so they act just like “passive immunisation” + have to be injected every couple of weeks
since they are normal proteins, their metabolism is NOT dependent on the liver/renal function - NO generic renal or hepatic toxicity
these are foreign protein, so the immune system on form antibodies against them
types of transplant rejection
hyperacute rejection
acute cellular rejection
acute vascular rejection
chronic allograft failure
hyperacute transplant rejection
time = mins-hrs
pathology = thrombosis+necrosis, tye 2 hypersensitivity
mechnism = preformed antibody + complement fixation
treatment = none
acute cellular transplant rejection
time = 5-30days
pathology = cellular infiltration, type IV hypersensitivity
mechanism = CD4 + CD8 T cells
treatment = immunosuppresion
acute vascualr transplant rejection
time = 5-30days
pathology = vasculitis, type II hypersensitivity
mechanism = de novo antibody + complemtent fixation
treatment = immunosupression +++
chronic allograft failure (transplant rejection)
time = >30days
pathology = fibrosis, scarring
mechanism = immune + non-immune mechanism
treatment = minimise drug toxicity, hypertension, hyperlipidaemia
what does vaccination produce?
memory in B cells + Tcells
longlived memory B cells are genereated during primary immune responses that can survive for many years - even after antigen has been eliminated
- memory B cells rapidly re-activate in response to a second encounter with that specific antigen
(clonal expansion, differentiation into plasma cells, antibody production)
what does vaccination stimulate?
rare naive T cells
indices a strong T-cell response in 14-21days
some become effector T cells which
- mostly die by apoptosis in absence of persisting antigen
- small number become MEMORY T CELLS + are maintained at low frequency
impact of memory on antibody production in primary vs secondary infection
primary = IgM first responds, then eventually IgG (clinical disease between these)
secondary = IgG kicks in before IgM + clinical features aborted
pros + cons of inactivated vaccines
pros -> quick + easy
- made quick, good antibody response, easy to store
cons -> not very potent
- require boosters (no clonal expansion + titres diminish over time)
examples of inactivated vaccines
whole cell vaccines
- polio, Hep A
- rabies, cholera
fractional vaccines
- subunit - Hep B, influenza, pertussis, HPV, anthrax
toxoids - diptheria, tetanus
pure polysaccharide vaccines - haemophilus influenza type B
pro / cons of live attenuated vaccines
pros
- all relevant effector mechanism elicited (antibody, AND activated T cells)
- localised, strong response
- usally only one single dose required
cons
- safety - may revert virulence, infection in immunocompromised
- must be stored/handled carefully
examples of live attenuated vaccines
viruses
- measles, mumps, rubella (MMR)
- chickenpox
- yellow fever
- rotavirus
- smallpox
- polio
bacterial - BCG, oral typhoid
DNA/RNA vaccines
DNA or RNA which directs the assembly of the antigenic protein inside the host cell
- can be given as “naked” DNA/RNA or packaged into a virus which then infects the host cells, instructing the cells to assemble the antigenic protein
DNA/RNA vaccine pros/cons
pros
- can be v potent
- easier to make than protein vaccines
- can be applied to target mutated proteins found in cancer (so calle d”neo-antigens”)
cons
- may require complex cold-chain
- so far no long term experience
examples of DNA/RNA vaccines
against covid19
- moderna vaccine (RNA)
- biontech vaccine (RNA_
- oxford vaccine (adenovirus)
virus like particles (VLP) vaccines
empty shells (capsids) made from viruses that look like the real virus but have no DNA/RNA
virus like particle (VLP) vaccines pros/cons
pros
- non-infectious
- v potent, one dose required
- activates both T + B cell responses
cons
- complex manufacture
- must be stored/handled carefully
examples of VLP vaccines
against papillomavirus assoc cancers
- cervarix, gardasil
against Hep B - engerix
