Ch3 - Immunity Flashcards
IL-1 major activities and clinical relevance
Activate T cells and macrophages, promote inflammation
Implicated in septic shock, RA, and atherosclerosis
IL-4 major activities and clinical relevance
Activation of lymphocytes, monocytes and IgE class switching Relevant for mast cells ensitisation, allergy and nematode infections
IL-5 major activities and clinical relevance
Differentiation of Eosinophils
MAbs against IL5 inhibit late phase eosinophilia in animal models
IL-6 major activities and clinical relevance
Activate lymphocytes, differentiation of B cells, stimulation of acute phase proteins
Acts as growth factor in myeloma and mesangial proliferative glomerulonephritis
IL-8 major activities and clinical relevance
Chemotaxis of neutrophils basophils and T cells
Levels increased in disease accompanied by netutrophilia
TNF α major activities and clinical relevance
promote inflammation
MAbs beneficial in in RA and crohns
What is the pathophysiology of chronic granulomatous disease?
failure to generate O2 in neutrophils and monocytes and inability to kill phagocytosed bacteria.
Which cytokines are responsible for fever?
IL-1 IL6 and TNFα
What are chemokines?
What are their receptors? What do they stimulate?
Substances that attract immune cells to areas where response is required.
G protein coupled receptors: activation results in extension of pseudopodia and therefore migration
What are the key triggers for each of the classic, mannose binding lectin pathway and alternative pathway for the complement cascade?
Classic: immune complexes
Mannose binding lectin: lectin binds mannose groups in bacteria
Alternative: viruses, bacteria, fungi, tumour cells
What are the 3 functions of the complement cascade?
Opsonisation, chemotaxis and lysis
Activate B cells and aid immune memory
Dispose of waste products
What are TLRs and what is their relevance in innate immunity?
TLRs act as pattern recognition receptors
Bacterial LPS produced by gram -ve organisms and CD14 bind to TLR4 leading to activation of gene transcription producing innate immune responses.
TLR5: flagellal
TLR 2: microbial lipoproteins
TLR9: bacterial DNA
TGF B major activities and clinical relevance
immunosuppression
Useful in MS and Myasthenia gravis
GMCSF major activities and clinical relevance
promotes granulocytes and monocytes
used to reduce neturopenia in chemo etc.
Interferon alpha major activities and clinical relevance
induces resistance to viral infection
Treats Kaposi sarcoma, chronic Hp b a nd C infection
Interferon beta major activities and clinical relevance
Induces resistance to viral infection
Reduces frequency and severity of MS relapses
What are the two key branches of acquired immunity?
Humoral: mediated by γ-globulin fraction of plasma proteins, major defense against bacterial infections
Cellular immunity: cytotoxic t cells attack and destroy cells bearing the antigen that activated, major defense against viral and fungal infections and tumors
What are some examples of antigen presenting cells and where are they located?
Langerhan’s cells: skin
Dendritic cells: lymph nodes and spleen
macrophages and b cells can function as APCs
Outline the pathway from APC ingestion of a protein to antibody production via B cells and Cell death via T cells
- APC ingests antigen, presents with MHC2 on cell surface
- MHC complex recognised by CD4 t cell
- IL2 autocrine activates to multiply CD4
- CD4 activates B cells via cytokines, and T cells via cytokines to produce antibodies in the former and to induce cell death via the latter
(MHC1 from APC can also activate the cytotoxic CD8 Ts)
What is the function of IgA
localised protection in external secretions eg. intestine
What is the function of IgG
complement activation
What is the function of IgM
Complement activation
What is the function of IgD
Antigen recognition by B cells
What is the function of IgE
Reagin activity: releases histamine from basophils and mast cells
List the contents of platelet granules and their key roles.
Granule 1: serotonin, ADP, secreted in response to platelet activation
Granule 2: secreted proteins
e.g PDGF: stimulates wound healing and vascular smooth muscle
e.g platelet activating factor: induces thromboxane and increases AA derivatives
Name some severe combined immunideficiencies (SCID) and describe where they act.
MHCI and MHCII deficiency (between t cell precursor and CD4/CD8
Hyper IgM syndrome (between Naive B cell and plasma cells)
X glinked agammaglobulinaemia (between B cell precursor and Naive B cell)
How do tacrolimus and cyclosporin work to prevent transplant rejection?
Prevent the dephosphorylation of NF-AT which is involved in the pathway between T cell receptor activation and gene transcription to release stimulatory cytokines.
What is the role of thrombopoeitin? Where is it produced? What does high serum thrombopoeitin mean?
Produced in liver.
Facilitates megakaryocyte maturation into platelets.
When platelets are LOW, less is bound and more is available to stimulate production.
What is the role of NFκB in the inflammatory response? What inhibits this?
Stimulated by cytokines, viruese and oxidants resulting in transcription of genes for inflammatory mediators. Inhibited by corticosteroids.
What are the acute phase proteins and when are they highest?
INCREASE CRP: day 0-5 Serum Amyloid A : day 0-7 Haptoglobin: day 7-14 Fibrinogen: day 10-14 C3: day 5-7
DECREASE
Albumin: day 5
Transferrin: day 5