Lymphoreticular & haemopoietic Flashcards
Describe MHC class I pathway
- Virus protein digested by Proteasome & peptide transferred to ER by TAP
- synthesised by host cell ER
- Once peptide bound transported to goli => cell surface
- Detected by CD8 T cell
describe MHC class II pathway
- Synthesised in ER and assocciated with invariant chain
- Invariant chain ensures that correct folding of MHC occurs and also blocks peptide binding groove so that viral proteins that will bind to MHC class I dont bind
- Enters vesicle & invariant chain is degraded and replaced by CLIP
- Endosome fuses with vesicle to form MIIC, CLIP removed and MHC transported to cell surface
- Present to CD4 helper cells
Only expressed on Antigen presenting cells
What are the differences in structure of the two MHC molecules
- MHC class I contains large transmembrane proteins alpha 3. stabilised by small B2 microglobulin. (alpha 1,2,3 and B2)
- MHC class II has two alpha and 2 Beta proteins
Role of dendritic cells
- Immature DC’s migrate to epithelial surfaces & ingest foreign antigen
- They migrate to LN via afferent lymph and take up residence in the paracortex as interdigitating dc’s presenting antigen to naie Tcells
How are MHC divers and what are the consequences of a lack of diversity
MHC is polygenic. there are 3x MHC class I & MHC class II genes. Also polymorphic
Lack of diversity means
- Infection ( not enough diversity in antigen)
- Vaccination
- Immune mediated disease - abnormal presentation of self peptides
Explain additional signal required by naive T-cells
Presence of infection causes expression of CD80/CD86 that amplifies the TCR recognition signal.
Require both MHC class I signal and CD80 to undergo clonal expansion and differentiation
what is the role of CD8 T cells
Cause virally infected cells to undergo apoptosis via
- Release of perforins and granzymes, triggering caspase cascade
- Fas ligand
- Cytotoxic cytotoxins
what are the roles CD4 Th1 cells
- secrete interferon gamma which provoke macrophages
- stimulate respiratory burst, procuding oxygen radicals, enhancing killing kapacity
- increased fusion of lysosomes to endosomes
What are the roles of CD4 Th2 cells
Secrete interlukin 4 (IL-4) which stimulates Bcells to differentiate into plasma cells. Also promote class switching
Explain why a unbalanced response in terms of T helper cells is sometimes required ?
- Interferon gamma inhibits TH2 and IL-4 inhibits Th1, helps to keep immune system in check
In the case of bovine TB, macrophages infected THEREFORE i biased Th1 response is required to eradicate. A biased Th2 response could lead to severe disease
What is the role of CD4+ Th17
Secrete cytokines that stimulate epithithelial cells to produce antimicrobial molecules. Clearing bacteria, fungi and yeasts
What is the role of Ntregs
Self reactive Tcells that have been reprogrammed. secrete IL-10 which supresses the prolifferation of Tcells. Regulatory function to reduce inflammation
How do cytokine receptors induce rapid response
JAK-STAT pathway
- Cytokine binds to its receptor causing Phosphorylation of JAK peptide
- Dimerisation of STAT
- Migrates to nucleus and acts as a transcription factor
How are various Ig isotopes produced
- Recombination of Variable heave genes (Vn) with a constant heavy (Ch) gene.
- The default combination will include either Delta (IgD) or Mu (IgM monomeric)
- B-cells activation via T-cells can cause class switching via change of the Ch gene but Vh is kept
What are the various Ig isotopes
IgD
- On surface of naive Bcells
IgM
- __present in monomeric form in naive b cells
- After activation, secretes in pentameric form, confined to circulation
- Potent activator of compliment
IgG
- Predominant Ig
- Activates virus neutralising antibodys
- activates compliment
- Binds to Fc receptors on phagocytic cells, acting as a opsinin
IgA
- Monomer in serum, Dimer in secretions
- Neutralises virus, bacterial adhesions and toxins
- mucosal immunity, secreted in tears, saliva, bronchial secretions, nasal secretions & small intestine muscosa
IgE
- Specifically binds to mast cells, causing degranulation
- serum levels raised in helminth parasite infection
Describe primary and response Ig responses
primary response
- Antigen first encountered, DC, B & T ells have a delay in engaging (lag). Bcells undergo clonal expansion/differentiation (log). Once class switching occurs Igm drops and IgG increases
Secondary response
- Circulating plasma cells are prepared for reinfection. Lag phase is shorter, IgG attains a higher concentration & percist for longer. Also Ig is predominant not Igm
Describe T cell dependant response
- B cell recognise antigen via surface Ig. Acts as an antigne presenting cell to MHC class II
- Th2 detects signal and releases IL-4 & interacts with CD40
- Class switching from IgM => IgG
describe T cell Independant response
- Bcells activated by bacterial PAMP e.g LPS
- Cause receptor antigen cross linkage whcih acts as a bcell mitogen
- Only stimulate primary response (IgM), No class switching or memory cells… Both dependant on tcells
How can you test for antibodys
Serology
- measuring Ig in the serum to determine immunity status
Immune assay
- Use labelled antibodys to determine presence of antigen
Enzyme linked immunesorbent assay (ELISA)
- sample of unknown amount of antigen is immobised
- The detection anti body is then added to form a complex
- The detetction anti body can be covalently linked to an enzyme or its self be detected by a secondary antibody
- between each step the plate is washed with a detergent to remove any protein or antibody that isnt specifically bound
- enzymatic substrate added to produce visible signal
Immunofluorescent antibody
What are the various Ig isotopes and their roles
IgD
- on surface of naive b cells. Antigen receptor for initiating b cell activation
IgM
- Present in monomeric form on naive b cells
- After b cell activated, pentameric form secreted
- predominant in early response acting as a aggulitin
- Potent activator of compliment
IgG
- Predominant Ig
- Important in virus neutralisation
- Activator of compliment
- Binds to Fc receptor on phagocytic cells acting as a powerful opsin
IgA
- Monomer in serum, dimer in secretions
- Neutralise virus, Bacterial adhesins & toxins
- Important in muscosal immunity, is secreated in tears, salivia, bronchal secretions, nasal secretions and SI
IgE
- Specifically bind to Fcepisilon receptors on mast cells causing degranulation
- Serum levels raised in helminth parasite infection
Upon infection, what occurs in the LN
- Naive b cells enter via HEV’s. Will encounter antigens on interdigital DC’s in paracortex
- If the opitope matches b cell receptor, begin to proliferate creating primary focus
- B cells interact with T cells to allow class switching
- Bcell then leave primary focus and enters follicle, creating a secondary follicle and germinal centre where proliferation occurs
- Bcells mature into plasma cells and migrate to medullary cords
- Some plasma cells migrate to other LN and some take up residency in bone marrow
