How does the Immune System Recognise Pathogens? Flashcards

1
Q

what is an immunogen?

what is an epitope?

A

immunogen: anything that elicits an immune response - most (but not all) antigens are immunogens

epitope: portion of antigen that is recognised and bound by a receptor on an immune cell

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2
Q

what is v basic overview of how antigen recognition occurs?

A
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3
Q

what is the capacity of innate immune cells, compared to adaptive immune cells, in no. of antigens recognised?

A
  • *innate**: recognise a few common microbrial structures that are present in microbes but not humans = few antigens can be recognised.
  • *adaptive (**lymphocytes - T/B cells): recognise millions of antigens. each individual T/B cell in body recognises different antigens - will be specific for single antigen
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4
Q

how do innate immune cells recognise antigens?

how do u describe innate immune cells’ response to self?

A

have Pattern Recognition Receptors (PRRs) recognise Pathogen Associated Molecular patterns (PAMPs) (structures found in microbes but not people - limited no. of structures)
- can be on surface, in lysosomes or cytoplasm

inherent lack of response to self (tolerance) - antigens arent present

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5
Q

what are Toll like receptors?

which TLR recognise flagella and LPS?

what happens as a response to TLR engagement?

A
  • *Toll-like receptors: examples of PRRs:**
  • TLR-5: recognises flagella
  • TLR-4: recognises LPS (on gram-negavtive bacteria)

get both them on plasma membranes and in lysosomes.

  • *TLR engagement:**
  • dimerization of receptor
  • activation of kinases
  • activation of TF
  • causes production of cytokines
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6
Q

wha

A
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7
Q

how do `T and B cells recognise antigens? - what does this mean with specificity?

A
  • each new lymphocyte only expreses one type of receptor and recognises only one type of antigen: means specificity is rare
  • *antigen introduced:**
  • only activates lymphocytes with correct receptor
  • lymphocytes clonal expansion -> expresssing same receptor
  • causes lots of daughters cells
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8
Q

how do B cells recognise antigens?

A
  • B-cells have recognition molecules called immunoglobins (Ig): often the eptiope is conformational
  • B-cells recognise antigens directly (without help of other cells)
  • activated B cells differentiate into plasma cells: secrete immunglogulin (‘antibody’)
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9
Q

what is the structure of an antibody?

A
  • *constant region:** same between different antibody molecules
  • *variable region:** differentates between the antibodies.
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10
Q

what are different classes of antibody?

what is specif

A
  • B-cells –> plasma cells: can make different classes of antibody (isotopes):
  • each antibody class can mediate different biological functions:
  • *antibodies**:
  • IgM
  • IgG
  • IgE
  • IgA

the specificity of these are identical (still recognise the antigen that was bound to B-cell), but the constant parts vary:mediating different biological functions

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11
Q
A
  • B cell always initially makes IgM - made in first in immune response but then swtiches to making IgG
  • IgG decreases but then increasees massively when have secondary response

- antibody specificity remains constant - whilst biological effector functions are varied

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12
Q

how is the great number of receptor diversity generated on antibodies?

A
  • each developing B cells expresses a distinct receptor
  • not different genes for millions of different receptors
  • INSTEAD: diversity is generated by mixing and matching gene segements within the heavy and light chain loci:

- Immunglobin heavy chain has:

a) V segments (40); b) D segments (25); c) J segments (6)
- get splicing of each of ^ to make lots of different genes: combinatorial diversity
- also: additional nucleotides can be added at the joints of ^^ to make more variation: junctional diversity

THEN:
any of immunoheavy chain stuff can associate with any of the light chains: more diversity: combinatorial diversity

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13
Q

how do t cells recognise antigens? what are the distinguishable features?

A
  • use **TCR - T cell receptor
  • T cells are presented antigens byantigen presenting cells (APCs):recogniselinear antigens
  • **The APC presents the antigen to the T cell using the major histocompatability complex (MHC)
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14
Q

how does antigen recognition differ between T cells and B cells?

A
  1. T cells: use APCs, B cells do not
  2. T cells recognise short, linear peptide antigens, B cells recognise conformational epitopes
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15
Q
A
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16
Q

what is the structure of T cell receptor like?

A
  • two chains: alpha and beta chains
  • both chains have a constant (same between all TCR) and a variable region (different: recognises different antigens)
  • antigen recognition with the peptide and MHC happens at the top
17
Q

what are the two types of T cells? what are their roles?

A
  • *CD4 T cells:** helper cells
  • *CD8 T cells**: cyotoxic cells
18
Q

how do we get such a wide variety of TCR diversity?

A

somatic DNA recombination (like in B cells)

get multiple variable regions (see slide) and get variable splicing

19
Q

which is the most potent APC?

A

dendritic cell

20
Q

what are the two types of MHC cells? which cells express each type?

A
  • *MHC Class 1:** expresed by all cells. made from:
  • alpha chain with 3 domains
  • peptide-binding cleft between a1 and 2 (see slide)
  • alpha chain is encoded by MHC.
  • alpha chain associates with B2 microglobulin
  • *MHC Class 2:** expressed by APC cells only
  • alpha and beta chains (both formed by cell)
  • peptide-binding cleft: formed from B1 and alpha1

Both have peptide-binding cleft: but the fit between the amino acid side chains inthe peptide and the grove of MHC molecule determine binding

21
Q

MHC Class I presents antigens to X?
MHC Class 2 presents antigens to X?

are they specific to one type of peptideS?

A

MHC Class I presents antigens to CD8 T cells
MHC Class 2 presents antigens to CD4 T cells

peptide binding by MHC molecules is promiscious - multiple peptides can be accomodated in the groove

22
Q

what are the properties of MHC that ensure the maximum number of peptides can be presented?

A
  • *1. MHC genes are polygenic:** more than one type of MHC class I and MHC class II molecule - can present slightly different range of peptides
  • *2. MHS genes are highly polymorphic:** multple alleles in the population mean that most people are heterozygous for MHC genes. (as a result - mother and father MHC genes are likely to be different - its this what is a barrier to organ transplant)

polygenic and polymorphic of MHC genes ensures mutlple different MHC molecules expressed, increasing the reportoire of peptides that can be presented

23
Q

how does coeliac disease occur

A
  • coeliac diease people undergo T cell response to gluten
  • only occurs in people carrying particular MHC class II molecules (HLA-DQ2 or HLA-DQ8)
  • only these MHC molecules can present gliadin peptides (in gluten) to T cells
  • gliadin peptides also acts as a substrate to tissue transglutaminsae (enzyme in GI): increases further the ability to bind to HLA-DQ2 or HLA-DQ8.
  • although necessary, if you have HLA-DQ2 or HLA-DQ8, don’t necessarily have CD.
24
Q

what is immunlogical tolerance?

A

immunlogical tolerance: the immune system attempting to eliminate self reactive cells that recognise self as antigens

removal during development: central tolerance
control when out in the body: peripheral tolerance