Clinical Immunology Flashcards
What is the name of sites in the body where immune system isn’t?
Immunoprivileged sites
How may cancer therapy be an immune therapy?
-Antibodies against regulators of imm system = cause overdrive of imm system - so own imm syst kills cancer cells
-Make genetically engineered antigen recs on T cells - so target cancer cells
What are immune checkpoints?
-Part of normal imm system
-Role = prevent imm resp being too large that healthy cells killed
-Imm checkpoints = occur when prots on T cells recognise & bind to partner prots of other cells e.g., tumour cell (= imm checkpoint prots) - when checkpoints & partner bind = ‘off’ signal to T cell - so cancer cell not killed
–> i.e., tumour cells have evolved to express ligands to down regulate imm resp
e.g., involves regulatory interaction between PD-1 (checkpoint prot) on imm cell & PD-L1 (partner prot) on tumour cell
What are immune checkpoint inhibitors?
E.g., ipilimumab & pembrolizumab
Block checkpoint prots binding w/ partner prot = so no ‘off’ signal - so T cell can kill cancer cells
How can T cells be genetically engineered?
Create gene - encodes antigen rec to recognise tumour cell - variable bit of antigen rec type - add activator parts on signalling tail of antigen rec on inside - transduce into T cells - readminister to patient - T cells will kill tumour cells
= CAR T-cell therapy
What factors of immune response must be controlled/regulated?
-Specificity
-Size of response
-Length of response
What is the immune system’s ‘balancing act’?
Responding to pathogens - but not to self or not too great a response to less harmful antigens/pathogens
What can stop regulation of the immune system’s balancing act?
-Infection
-Genetic factors
What happens if immune system’s ‘balancing act’ is lost?
-Too great a response = damage to self –> autoimmune/autoinflammatory disease
-Too low a response = greater susceptibility to infection/cancer –> immunodeficiency
What may occur in immunodeficiencies?
-Cells can’t kill bacteria they take up
-Immunodeficiencies related to TFs - so can’t make certain CD4+ T cells - can’t activate macrophage
-Complement may not be activated
What is immunodeficiency?
Lack of function of components of imm system = more susceptible to infection and or cancer - particular susceptibility based on deficiencies
What are the 2 types of immunodeficiency?
-Primary
-Secondary
What is primary immunodeficiency?
-Often from birth
-Due to genetic muts
What is secondary immunodeficiency?
-Often not from birth
-Due to environmental factors - e.g., infection, chemotherapy (chemicals destroy BM - not lots of imm cells), severely malnourished (can’t make imm cells)
What occurs in primary immunodeficiency patients, & what can this be used for?
-Have knocked out genes of imm syst
-Tells us how important these gene components are –> shows role of certain components of imm syst
What are severe combined immunodeficiency patients i.e., ‘bubble babies’ & how is it caused?
-NO T OR B cells –> so NO adaptive immunity
-Due to loss of function mutations in RAG gene (need this for somatic hypermutation - to make functional gene) - so can’t make functional antigen rec gene - as RAG is part of large prot complex responsible for cutting out gene segments & putting back together
–> can’t rearrange at antigen rec locus = no functional antigen rec gene
What used to be done for severe combined immunodeficiency patients, & what is done now?
Used to = put in bubbles to shield
Now = give prophylactic antimicrobials - so don’t get fungal bacterial viral infections
–> transplant w/ new imm syst from healthy person - appropriate match (done in young children = v. high success rate)
What causes Mendelian Susceptibility to Mycobacterial Disease (primary immunodeficiency)?
-Th1 cells can’t function = no IFNy (can’t activate macrophages)
-Stop Th1 cells being made
–> due to genetic defects
-SO GET LOTS OF MYCROBACTERIAL DISEASES
What causes X-linked IPEX disease - autoimmunity (primary immunodeficiency)?
-Foxp3 - TF for Treg - needed or function - on X chromosome - so get autoimmune responses to all endocrine organs
Caused by mutations in FoxP3 gene - causing dysfunction of Tregs
Death within first couple of years of life
Neutrophil facts?
-Neutrophils made in BM = short-lived (8-24hrs) but abundant
-At forefront of infection control of bact & fungi @ barriers w/ ext env
What causes neutropenia?
-Diseases of BM
-Radiation
-Chemotherapy
-Some infections
-Autoimmune diseases
= secondary immunodeficiency
What is neutropenia (secondary immunodeficiency)?
-At risk of opportunistic infections = where contract infections from organisms people w/ functional imm syst would not be infected w/
–> is an immunodeficiency!
Examples of organisms harmful to people with neutropenia (as risk of opportunistic infections)?
-Staphylococcus aureus
-Escherichia coli
-Pseudomonas aeruginosa
-Aspergillus fumigatus
(normally wouldn’t be classified as pathogens)
What is G-CFS therapy?
Treatment for neutropenia - but requires functional bone marrow
What is autoimmunity?
Lost regulation - & have overactivity of imm syst = damage to self
-Adaptive imm syst targets self-antigens leading to inflamm & destruction of body tissue
–> so won’t ever resolve as self-antigens always present
–> tissue destruction & inflamm cause DAMPs signal to cause more inflamm = cycle
What is involved in the acute response on re-exposure an allergen?
-Made IgE antibodies (constant portion) = bind to Fc epsilon recs on mast cell surface –> allergen cross-links multiple antibodies bound recs = strong signalling
-Mast cell degranulates - releases histamine & lipid mediators = causes wheezing, sneezing, conjunctivitis…
What is the damaging role of systemic chronic inflammation (causes & consequences)?
Lots of inflamm can predispose to many diseases (inflamm & immunity = link to many diseases - not just autoimmune ones)
