Lymphoreticular & haemopoietic Flashcards

1
Q

Describe MHC class I pathway

A
  • 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
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2
Q

describe MHC class II pathway

A
  • 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

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3
Q

What are the differences in structure of the two MHC molecules

A
  • 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
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4
Q

Role of dendritic cells

A
  • 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
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5
Q

How are MHC divers and what are the consequences of a lack of diversity

A

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
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6
Q

Explain additional signal required by naive T-cells

A

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

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7
Q

what is the role of CD8 T cells

A

Cause virally infected cells to undergo apoptosis via

  • Release of perforins and granzymes, triggering caspase cascade
  • Fas ligand
  • Cytotoxic cytotoxins
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8
Q

what are the roles CD4 Th1 cells

A
  • secrete interferon gamma which provoke macrophages
  • stimulate respiratory burst, procuding oxygen radicals, enhancing killing kapacity
  • increased fusion of lysosomes to endosomes
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9
Q

What are the roles of CD4 Th2 cells

A

Secrete interlukin 4 (IL-4) which stimulates Bcells to differentiate into plasma cells. Also promote class switching

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10
Q

Explain why a unbalanced response in terms of T helper cells is sometimes required ?

A
  • 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

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11
Q

What is the role of CD4+ Th17

A

Secrete cytokines that stimulate epithithelial cells to produce antimicrobial molecules. Clearing bacteria, fungi and yeasts

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12
Q

What is the role of Ntregs

A

Self reactive Tcells that have been reprogrammed. secrete IL-10 which supresses the prolifferation of Tcells. Regulatory function to reduce inflammation

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13
Q

How do cytokine receptors induce rapid response

A

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
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14
Q

How are various Ig isotopes produced

A
  • 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
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15
Q

What are the various Ig isotopes

A

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
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16
Q

Describe primary and response Ig responses

A

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
17
Q

Describe T cell dependant response

A
  • 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
18
Q

describe T cell Independant response

A
  • 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
19
Q

How can you test for antibodys

A

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

20
Q

What are the various Ig isotopes and their roles

A

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
21
Q

Upon infection, what occurs in the LN

A
  • 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