Immunology Flashcards
which cytokines stimulate CRP production
IL-1 and Il-6
deficiency of which complement component is associated with most severe pyogenic infections
C3
Role fo C3B
opsonisation
Role C3a and C5a
anaphylotoxins- generate chemotaxic gradients; mediate phagocyte migration to area
Role of C5-C9
membrane attack complex
Osmotic lysis of microbe
most common complement deficiency
C2
which complement defiicnecy most associated with SLE
C1
which complement deficinecy is most associated with Nesseria infections
C5-C9
what do CH50 and AH50 test for
activity of classical and alternative complement pathways respectively
Drug reaction with eosinophilia and systemic symptoms (DRESS)
severe adverse drug reaction, up to 2-8 weeks after offending drug
T cell mediated hypersensitivity (type 4)
Usually carbamazepine, phenytoin, lamotrigine, allopurinol, vanc, sulfonamide abx
Characterized by:
-extensive skin rash, mucosal involvement in 50%, usually rash very widespread
- fever
-lymphadenopathy
- eosinophilia
- leucoytosis
neutrophilia
- liver injury with abn LFTs
Rx: if severe: glucocorticoids
GVHD
GVHD occurs when lymphocytes from donated blood are either not recognised by the patient or the patient’s immune system is unable to destroy them. The skin, bone marrow, and gastrointestinal track are most often affected. It occurs 4-30 days after transfusion but usually occurs in the second week post transfusion. It is rare and difficult to treat but can be prevented by the use of irradiated blood products.
Children with immunodeficiency (either primary or secondary to chemotherapy), haematological malignancy or haematopoeic cell transplantation, and premature low birth weight babies are at risk. Children in these groups should receive irradiated blood.
Biopsy: satellite dyskeratosis
Presents with fever, rash, diarrhoea, hyperbilirubinemia, cholangitis , deranged LFTs
difference between TREC and KREC
TREC is a by-product of the T-cell receptor gene recombination- used for SCID, di george, CHARGE, ataxia telangiectasia
KREC is a by-product of the B-cell receptor recombination- used for XLA
T cell development
BM–> thymus for t cell university
Initially double negative
Then double positive - CD4+CD8+
Positive selection- recognise MHC I or II (only survive if bind moderately)
Negative selection- recognise self antigens presented on MHC but dont bind too strongly (or this would cause autoimmunity)
Class depends if they recognise antigen on MHC1 (become CD8) or MHC2 (become CD4)
Then once they are either CD4 or CD8 they leave the thymus as naive T cells and go into the lymph nodes to wait for antigen presenting cells
T helper cell subsets
which cytokine causes T cell proliferation
Il-2
which cell type is IL-2 mainly secreted by ?
CD4 Th cells
what is the immunophenotype of most common type of SCID
T-B+NK-
(x linked, IL2Rg mutation encoding IL-2 receptor gamma chain)
what does IL-2 do?
Produced by CD4 Th cells
Promotes T cell proliferation
Differentiation of T cells into regulatory T cells and memory T cells
Stimulates naive CD4 T cell differentiation into Th1 and Th2 cells , reduces differentiation into Th17
Increases cell killing activity of NK cells and cytotoxic T cells
which 2 immunoglobulins can fix complement
IgM, IgG
what cell types do IgE bind to?
mast cells and basophils
DDx hypogammaglobulinemia
Excessive loss- A1AT ( losing in gut), nephrotic syndrome, intestinal lymphangiectasia
BUT even if losing IgG, unlikely to be able to lose IgM as such a big molecule
why is pneumovax 23 not a very effective vaccine?
polysaccharide vaccine
T cell independant
Mainly IgM produced
Relatively short lived plasma cells
there is a particularly poor polysaccharide response before 2 years
B cell maturation
Th2 cells release which cytokines
Il-4, Il-5, Il-13
Th1 cells release which cytokines
IFN-y
Il-2
which target macrophages
Th17 cells release which cytokines
Il-17
Il-22
these target neutrophils
Role of IL-12
Released by APC (macrophages, dendritic cells) and drives the differentiation from undifferentiated T helper cells to Th1 cells
Also activates NK cells, which secrete IFN-g which also promoted Th1 cell development
*Th1 cells also secrete IFN-g which amplifies differentiation of other Th1 cells, also NK cells produce IFNg
Role of interferon gamma
Released by Th1 cells, CD8 T cells, and NK cells
Activates macrophages and makes them better at killing pathogens
Promotes secretion of IL-12 to maintain positive feedback loop
Increases production of TNF-a
Role of IL-1
Produced by macrophages/dendritic cells
Pro inflammatory cytokine
Chemokine production –> increases migration of phagocytes to site of infection, vasodilation
Endogenous pyrogen –> fever
Role IL-3
Growth factor for hematopoeitic stem cells
Regulates the growth and differentiation of hematopoietic progenitor cells and functionally activates mature neutrophils or macrophages.
Role IL-4
Differentiation of Th0 cells into Th2 cells
Promotes B cell activation and class switching to IgE
Role IL-5
Activation of eosinophils
Class switching to IgA
Role IL-6
Proinflammatory cytokine released by macrophages in response to PAMPS
Mediates fever and acute phase response as well as the production of neutrophils in the bone marrow.
It supports the growth of B cells and is antagonistic to regulatory T cells.
It is capable of crossing the blood–brain barrier and initiating synthesis of PGE2 in the hypothalamus, thereby changing the body’s temperature setpoint.
cell marker on hematopoetic stem cells
CD34
what receptor do all T cells have
CD3+
Activation of naive T cell
T cell receptor binds to antigen on MHC I or 2
Costimulation - CD28 on T cell binds to B7 on APC
Once both signals received, Th cells increase expression of IL-2 and IL-2 receptors (autocrine signal) causing clonal expansion and proliferation/differentiation into Th1 and Th2 cells
what cell surface marker do all leukocytes share
CD45
Th17 cells role
Fights some extracellular bacteria eg Klebsiela, Neisseria, Staph aureus and fungal infectins
Secrete IL-17 and IL-22
Hyper IgE (Jobs syndrome) due to impaired Th17 differentiation
Regulatory T cells
Suppress CD4, CD8 cells, B cells and NK cells
Differentiation driven by TGF-beta
Produce IL-10 and TGF-b
Cell surface receptors: CD4, CD25
TGF beta
inhibitory cytokine
Released by many lymphocytes and macrophages
Drives differentiation of Th cells to T reg cells
IL-10 role
anti-inflammatory cytokine secreted by macrophages + T reg cells
IL-10 suppresses many functions of natural killer (NK) cells and T cells, primarily by preventing antigen-presenting cells (APCs) from producing proinflammatory cytokines, such as IL-12, and from up-regulating molecules involved in antigen presentation and lymphocyte activation
what are the main cytokines produced by Th1 cells
IL-2
IFN-gamma
—> macrophage activation
Activation and proliferation/differentiation of Th cells
Activation of cytotoxic T cells
Class switching to IgG
Role IL-13
Mucous production and peristalsis of gut to help remove helminths/parasites
Role T follicular helper cells
Found in lymph nodes
Produce IL-21 –> drives B cell proliferation
Tfh play an essential role in the formation of germinal centres (GCs), B cells within GCs undergo rapid proliferation and antibody diversification, allowing the production of many types of antibody + differentiation into memory B cells
Role of IFN-g
Macrophage stimulation
Produced by helper T cells, cytotoxic T cells and NK cells
what % of kids outgrow a peanut allergen by adulthood
20%
14% for tree nut allergy (lowest)
hypersensitivity reactions
Type 1- IgE mediated
Type 2- IgG/IgM mediated (eg transfusion reaction, autoimmune hemolytic anemia, Graves, Goodpastures, myasthenia gravis)
Type 3- immune complex deposition (eg SLE, serum sickness, glomerulonephritis)
Type 4- T cell (eg contact dermatitis, tuberculin reaction, T1DM, multiple sclerosis, rheumatoid arthritis)
STAT3 mutation
Hyper IgE syndrome
antibody associated with anterior uveitis in JIA
ANA
enthesis associted anterior uveitis
HLA B27
