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FunMed Immunology > How does the immune system recognise pathognes > Flashcards

How does the immune system recognise pathognes Flashcards

1
Q

what is an antigen

A

anything that binds to a specific receptor on an immune cell (generates antibody)
- Antigens can be bits of bacteria, viruses, pathogens contain many antigens, antigens can also be part of out own body (self antigen)

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2
Q

what is an immunogen

A
  • This is anything that elicits an immune response

- Most but not all antigens are immunogens

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3
Q

What is the epitope

A
  • This is the portion of an antigen that is recognised and bound by a receptor on an immune cell
  • Antigens can contain many epitopes
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4
Q

why do we have an immune system

A

to protect us against pathogens and disease

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5
Q

what is the challenge of the immune system

A
  • does not know which pathogen it will encounter in advance
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6
Q

why are we attractive to pathogens

A
  • warm
  • wet
  • nutrients
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7
Q

which is older the adaptive or innate immune system

A

innate

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8
Q

what must the immune system do

A
  • must discriminate between self and non self (foreign)
  • recognises and response to pathogens, if this fails then you get death from infectious disease
    but if you response to components of your own body then you get an autoimmune system
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9
Q

overview of antigen recognition

A
  1. Receptor binds to antigen - this is how it recognises that its there
  2. This will cause a signalling cascade
  3. This goes to the nucleus and changes gene transcription
  4. This leads to the production of effector molecules such as antibodies and cytokines
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10
Q

what ate the cells that make up the innate immune system

A

NK cells
macrophages
dendritic cells
granulocytes such as neutrophils

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11
Q

can adaptive or innate recognise a limited range of antigens

A

innate

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12
Q

How does recognition of pathogens happen by innate immune cell

A
  • Pattern Recognition Receptors (PRRs) recognise pathogen associated molecular patterns (PAMPs)
  • PAMPs structures are lacking in our own body but they are present on pathogens
    these structures
  • flagella
  • lipopolysaccharide cell wall
  • ssRNA/dsRNA genome
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13
Q

what are PAMPs

A
  • These are structures that are found in microbes but they are not found in people
  • limited structures - they have a small number of receptors
  • lack of response to self is insert as our cells to have flagella, so there is not a response from the innate immune system to our own tissues
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14
Q

what are examples of PAMPs

A

they can be bits of cell walls or flagella

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15
Q

one innate immune cell can ..

A

one innate immune cell can express a number of different PRRs and therefore response to a number of different things

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16
Q

describe features of the innate immune system cells

A
  • limited structures - they have a small number of receptors
  • lack of response to self is insert as our cells to have flagella, so there is not a response from the innate immune system to our own tissues, for example this is because our cells do not have cell walls or flagella
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17
Q

what are an example of PRRs

A

Toll like receptors - so therefore they recognise PAMPs

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18
Q

how many TLR(toll like receptors) do humans have

A

10

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19
Q

where were toll like receptors identified in

A

fruit fly

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20
Q

what is the structure of Toll like receptors

A
  • Horse show Luciene rich repeat
  • extracellular domain that interacts with the molecule
  • tear domain that interacts with the signalling domain
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21
Q

why to lymph nodes get swollen

A

due to clonal expansion

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22
Q

recognition of antigen by B cell

A
  • the antigen recognition molecules are used by B cells are immunoglobulin (Ig)
  • the membrane bound Ig functions as the B cell receptors
  • antigens are recognised directly as there is a direct interaction between the BCR and the antigen, they recognise the shape of the protein - they are recognised by there epitope
  • when this occurs B cell becomes activated and becomes plasma cell
  • plasma cells secretes a soluble form of the B cell receptor into the environment
  • soluble form of the B cell receptor is called the antibody
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23
Q

structure of an antibody

A
  • heavy chain
  • light chain
    Variable region
  • this is the region that is involve din antigen binding
  • this is the region that is different between different antibody molecules because they vary they can bind to different antigens, made from a heavy chain and a light chain
  • both variable regions are the same
    Constant region
    – things that are the same in every antigen molecule – determines its biological functions as it controls what the antibody does
  • Disulphide bonds bind two parts of the chaisn together
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24
Q

B cells can make ..

A

different classes of antibody (isotopes)

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25
Q

what are the types of antibodies made

A
  • IgM
  • IgG
  • IgE
  • IgA
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26
Q

How do B cells undergo class switching

A 
When a B cell first makes plasma cells and these makes antibodies the first type of antibody made is an IgM
- class switching occurs this means that the B cell that initially makes IgM can switch and make a different type of antibody for example it starts to make IgG 
During this 
- antibody constant region remains the same 
- but the biological affection functions are varied
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27
Q

what type of structure is IgM

A

pentriometric strucutre

28
Q

What happens in the primary immune response

A 
IgM originally produced (if IgM is high in the blood then infection is recent)
class switching IgG produced (if IgG is in the blood infection was a while ago)
29
Q

what happens in secondary immune response

A

IgG is just produced

30
Q

How is receptor diversity generated

A
  • Each developing B cell expresses a distinct receptor
  • Don’t have a gene for each receptor otherwise there would be millions of genes
  • ## Diversity is generated by mixing and matching gene segments within the heavy chain and light chain loci
31
Q

what is the mechanism of the somatic DNA recombination (heavy chain) - developing receptor diversity

A

V segment (40), d segments (25) and j segments (6)is what it contains

  • In B cells as they develop in the bone marrow a recombination even occurs
  • This leads to a splicing out of a region of DNA that leads to the D region and J region joining together, it is random which D segment and which J segement is put together
  • Second recombination event occurs, this is when the V region joins to the DJ region
  • Transcirpiton of that gene takes place, forms mrna this is then spliced to get rid of the exons
  • Then translated to form the heavy gene
  • the process is tightly regulated
32
Q

how many in the V segment

A

40

33
Q

How many in the J segment

A

6

34
Q

how many in the D segment

A

25

35
Q

how do T cells recognise antigens

A
  • they use a T cell receptor
  • antigen is presented by an antigen presenting cell (dendritic cell and macrophages)
  • they recognise linear peptide antigens that are presented on APC cells in the MHC molecule on the cell surface membrane
36
Q

what is on the surface of the APC

A

MHC (major histocompatibility complex)

37
Q

what does the antigen peptide interact with when signalling T cells

A

the TCR and the MHC on the APC

38
Q

describe the structure of the TCR

A
  • made up of alpha and beta chains
  • have a variable region
  • have a constant region
  • have stalk segment joins it to the cell surface membrane
  • disulphide bond links the alpha and beta chain together
  • have a short cytoplasmic cell so on the surface of theT cell it has to form ac complex with other molecules to mediate signalling events
39
Q

where is the precursor of T cells made

A

in the bone marrow

T cells are made in the thymus

40
Q

what does CD stand for

A

cluster of differentiation

41
Q

whats the difference between CD4+ and CD4

A

CD4+ has the TCR receptor whereas CD4- does not

42
Q

how do we generated T cell receptor

A
  • process of recombination
  • same process as B cell
  • but genes for alpha and beta chain not the heavy and light chain like in B cell
43
Q

what is a MHC

A

the major genetic region that determines the compatibility of tissues transplanted between individuals

44
Q

What are the two types of MCH

A

MHC Class I and MHC Class II

45
Q

define HLA

A

human leukocyte antigens it is an MHC

46
Q

describe the structure of MHC class I and II

A
  • Both bind to peptide
  • have a peptide cleft which allows it to bind to the peptide
    MHC 1 -3 alpha 1 beta, cleft formed from alpha 2 and alpha 1
    MHC II - 2 beta and 2 alpha, cleft formed from Beta 1 and alpha 1
47
Q

describe an example of MHC

A

HLA - this is just the animal specific name

48
Q

where is MHC I

A

on all cells in the Body that are nucleated

49
Q

MHC class I presents..

A

presents its peptide antigens to cytotoxic T cells

50
Q

MHC class II presents…

A

presents its peptide antigen to a CD4 cells

51
Q

why is peptide binding in MHC molecules promiscuous

A

they bind a range of peptides that can be accommodated in the groove (not a single specific peptide)

52
Q

how many different MHC class I molecules are there

A

3

53
Q

How many different class II molecules are there

A

2

54
Q

what are the properties of MHC

A

MHC has two properties that help ensure the maximum number of peptides can be presented
it is
- polygenic
- polymorphic - this is multiple variants of each gene within the population

55
Q

polymorphic proterites

A

for each of the loci there are multiple different versions of each of the gene within the population

  • therefore it is highly unlikely that the mother and father will have the same version therefore we are heterozygous at the MHC loci
  • multiple genes coding for MHC1 and 2
56
Q

what is a barrier to organ transplantation

A

polymorphism, different MHC molecules on the graft are recognised as foreign and tissue rejected due to the immune response

57
Q

what does the polygenic and polymorphic MHC genes ensure

A

multiple different MHC molecules are expressed increasing the repertoire of peptides that can be presented

58
Q

describe coeliac disease

A
  • Relatively common
  • Chronic inflammation of small intestine - don’t absorb nutrients properly
  • Inappropriate immune response to wheat gluten
59
Q

Describe the immunology of coeliac disease

A
  • Only occurs in people carrying particular MHC class II molecules – HLA-DQ2 OR HLA-DQ8, if you don’t have HLA molecule you will never develop coeliac disease
  • Only these MHC molecules can present gliadin peptides to T cell to cause disease
60
Q

Describe the immunology of coeliac disease

A
  • Only occurs in people carrying particular MHC class II molecules – HLA-DQ2 OR HLA-DQ8, if you don’t have HLA molecule you will never develop coeliac disease
  • Only these MHC molecules can present gliadin peptides to T cell to cause disease
  • tissue transflutaminase modifies gliadin which helps it bind even better to these MHC molecules
61
Q

what are the two types of tolerance

A

central tolerance

peripheral tolerance

62
Q

what is central tolerance

A

– as T cells develop in the thymus (and B cells in the bone marrow) their receptors are tested for reactivity to self antigens, if the self reactivity is too strong the lymphocytes are killed

63
Q

what is peripheral tolerance

A

self reactive lymphocytes that escape deletion during development can be controlled in the periphery ( e.g. by regulatory T cells – Treg)

64
Q

what happens when you failure to discriminate self from non self

A
  1. death from overwhelming infectious disease

2. autoimmune diseases

65
Q

what happens with the innate immune cells recognise pathogen

A
  1. They release pro-inflammatory cytokines and chemokine this leads to inflammation and recruitment of more immune cells
  2. They begin to non-specifically phagocytose the pathogens
  3. Antigen-presenting cells travel to the secondary lymphoid organs to present antigens (using MHC) to the adaptive immune system
66
Q

what kind of antigens does MHC class 1 deal with

A

endogenous antigens

67
Q

what kind of antigens does MHC class 2 deal with

A

exogenous antigens

FunMed Immunology (6 decks)

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