Dunedin-Immunology Flashcards
What does the innate immunity include?
complement
phagocytosis
the acute phase proteins
NK cells
T and B cells NOT involved- exception IgM antibodies produced by the B1 CD5* subset
What is the innate response to intracellular infections?
and then adaptive B?
NK cells, cytokines, macrophages
Adaptive –> T cells –> B cell –> antibody
What is the innate response to extracellular infections? and then adaptive
polymorph cells and complement
adaptive: b-cell and antibody
What are 3 key cytokines macrophages produce?
IL-8 (recruitment cytokine)
TNF alpha (changes vasculature and goes to liver to produce acute phase proteins)
IL-1 (goes to hypothalamus and changes temperature set)
Describe the three complement pathways
What protects host cells against complement?
DAF (decay accelerating factor) and MCP(membrane cofactor protein) which break down C3 convertase
HRF (homologous restriction factor) C8 binding protein and CD59 which prevent the formation of MAC on host cells
What is the primary function of C3b?
opsonisation
Which immunoglobulin can activate the complement cascade?
IgG and IgM
IgM + C3b can bind to C3b receptors
What is an epitope?
Part of an antigen recognised by the antigen combining site of an antibody (paratope) or a T cell receptor.
What are toll like receptors?
they are receptors used by dendritic cells to determine ‘danger’
What chromosome is HLA (MHC) molecules encoded on?
chromosome 6
What is MHC class 1 and where do you find it?
Class 1, A, B, C, E.
on nucleated cells
What is MHC class 2 and where do you find it?
DP, DQ, DR
ONLY on antigen presenting cells
What is MHC Class 3?
HSP70, complement 2 and 4
Which interleukin causes proliferation of T cell?
IL-2
What is the difference between endogenous and exogenous pathway regarding MHC?
endogenous –>present via MHC Class 1
exogenous –> presents via MHC Class 2
List the T helper subsets and what cytokines they produce
TH1- interferon gamma, IL-12
TH2- IL-4, IL-5, IL-13
TH17- IL-17, IL-22
What immunoglobulin is on surface of naive B cells?
IgM
Describe the B subsets
Which B subset undergoes class switching?
B1- independent, IgM isotope, no memory cell, identified by expression of CD5 cell surface marker
B2 subset, undergoes class switching, produces memory cells
do NOT express CD5
Which antibody can cross the placenta?
IgG
Describe the different types of Hypersensitivity reactions
Type 1 - IgE mediated, IL-4, mast cell degranulation. E.g anaphylaxis
Type 2- IgG mediated. antibody mediated. e.g incompatible blood transfusion, hyperacute graft rejection, thyrotoxicosis
Type 3- IgG mediated, immune complex C3a and C5a. complement activation. eg anaphylactoid reactions
Type 4- cell mediated. eg contact dermatitis, TB, chronic granuloma
What do C5-C9 deficiencies usually cause?
encapsulated bacteria such as neisseria infection
What does T cell deficiency manifest as?
Poor response to fungal, viral and intracellular bacteria
eg of T cell deficiency –> Di George
What is the effect of B cell deficiency?
pyogenic infections (reduced opsonisation by antibody –> impaired phagocytosis)
What are the main mutations causing SCID?
ADA mutation (adenosine
Common Cytokine gamma receptor mutation
RAG mutation
What activates the complement system?
alternate pathway –> toxins, some acute phase proteins
lectin pathway –> sugars
Classical pathway:
- aggregated immunoglobulin
- C-reactive protein
- poly anions and cations e.g. heparin
- staphylococcal protein A
- some RNA viruses
- some proteolytic enzymes
What do Natural Killer cells look for?
absence of MHC 1, lack of killer inhibitor on cell surface
if not present, will cause apoptosis
What is the main role of dendritic cells? describe what they bind to
antigen presenting cells
phagocytosis
they prime T cells
CD40 (with CD40L on naive T cell)
MHC-II (with TCR, and CD4)
CD80/86 (with CD28 on naive T cell)
Describe the structure of MHC 1 compared to MHC 2
MHC1 is smaller, 3 alpha chains and a B2 microglobulin
MHC2 is bigger, alpha and beta chain. THIS IS SIMILAR TO A T CELL RECEPTOR
Which MHC class does T helper cells recognise?
MHCII
What is the role of IL-2?
causes proliferation of T cells
When can B cells undergo class switching?
when a B cell binds to CD40 ligand
Describe the structure of an immunoglobulin
idiotype is specific to the antigen
heavy chain gene segments: V,D,J, C
light chain gene segments: V, J, C
heavy and light chain together produce antigen combining site.
What is somatic hypermutation?
the process in which antibody class switching occurs and changes specificity
What is the difference between affinity and avidity?
affinity is how strongly it binds
avidity is how many sites we bind on an antigen
What bacteria give you post-splenectomy infections?
step pneumonia
nesseria meningitis
haemophilis influenza
What is hyper IgM syndrome and what is it caused by?
normal or elevated levels of IgM with reduction in IgG and IgA
Caused by deficiencies with:
CD40L deficiency
CD40 deficiency
activation- induced cytidine deaminase (AID) deficiency
Uracil DNA glycolase deficiency
What is bare lymphocyte syndrome?
Caused by MHC-II deficiency –> cannot activate CD4 T cells –> susceptible to fungal and viral infection
Describe the co-factors required in HIV
Infection via gp120 envelope glycoprotein of HIV RNA retrovirus binding to CD4
cofactor required:
- CCRF
- CXCR4
- Methotrexate used in RA and other inflammatory diseases. Which enzyme does methotrexate inhibit ?
A) Dihydrofolate reductase
B) Dihyroorotate reductase
C) Inosine monophosphate dehydrogenase
D) Thiopurine methyltransferase
A) Dihydrofolate reductase
dihydroorotate reductase –> leflunomide
Inosine monophosphate dehydrogenase –> Mycophenolate mofetil (used in transplant and autoimmune diseases).
Thiopurine methyltransferase: Azathioprine, 6-mercaptopurine (used in IBD, RA, and other autoimmune diseases).
- What is the main mechanism of action of metaraminol?
A) Alpha 1 agonist
B) Alpha 2 agonist
C) Beta 1 agonist
D) Beta 2 agonist
A) Alpha 1 agonist