W2 Adaptive immunity Flashcards

1
Q

Normally is innate immunity successful or not successful?

A

Majority of the time innate immunity successfully removes pathogen and the adaptive immune system is not needed.

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2
Q

What cells are involved in adaptive immunity?

A

Lymphocytes and plasma cells
Dendritic cells and APC in the transition from innate to adaptive.

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3
Q

What is the overview function of T cells and B cells?

A

Recognise specific antigens
Proliferate and mediate effector function
Provide immunological memory.

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4
Q

What is an antigen?

A

Part of the pathogen to which T cells and B cells respond.

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5
Q

What are lymphocyte antigen receptors like?

A

Highly specific, made of variable and constant regions.
Enormous diversity in receptors by cell.
T cell - TCR
b cell - BCR

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6
Q

What are the different effector function of T cells?

A

Cytotoxicity
Help of other immune cells
Regulation - turning off innate immunity.

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7
Q

What are the different effector function of B cells?

A

Become plasma cells to secrete antibodies

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8
Q

Where are adaptive immune responses co-ordinated?

A

In secondary lymphoid organs.

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9
Q

Explain the development of T cells?

A

Originate in the bone marrow
Mature in the thymus
Respons and become active (not naive) to antigens presented to it.

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10
Q

What is the structure of a TCR?

A

Heterodimeric receptor, made of alpha and beta chains.
Each chain has a constant region and a variable antigen binding region.

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11
Q

Explain how recombination creates diversity in TCR and BCR?

A

Genes coding for the receptors has many varying segments, segments are separated.
Large protein complex randomly cuts out sections and reorganises to form a continuous gene, during this process new nucleotides may also be randomly introduced at the segment junctions.
Creates a wide variation of results.

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12
Q

How does the body filter out cells that would attack self cells?

A

Occurs in place of maturation b (bone marrow), t = thymus.
Whilst maturing are surrounded by proteins that are found in abundance in the body, t/b-cells that bind to a self protein are destroyed.
Acts as a double lock system as even if a self b-cell is not destroyed the self t-cell needed for action likely was destroyed.

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13
Q

What is an epitope?

A

The part of an antigen that is recognised by the immune system.

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14
Q

What are the two main types of T-cell?

A

Helper T-cell CD8+
Cytotoxic T cell CD4+

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15
Q

What are some key properties of a Cytotoxic T cell ?

A

Responds to MHC1 which presents on all nucleated body cells
Co-receptor to MHC1 is CD8
Kills virus infected cells directly

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16
Q

What are some key properties of Helper T Cells?

A

Responds to antigens presented by MHC2 only found on professional antigen-presenting cells
Co-receptor to MHC2 is CD4
Produces cytokines to activate immune cells and expressed surface molecules to affect other cell types.

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17
Q

Explain the application of t cells and MCH receptors.

A

MHC receptors display part of antigen from within an APC to the surface.
CD4 helper cell interacts with MHC2 binds to lateral edge, TCR then binds directly to presented epitope
CD8 cytoxic interacts with MHC1 binds to lateral edge, TCR then binds directly to presented epitope

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18
Q

What are some key features of dendritic cells?

A

Present both MCH2 and 1 so can activate cytotoxic and helper t cells.
Is a professional antigen-presenting cell
They mature when stimulated by PAMPs and DAMPs
They migrate to secondary lymphoid tissue once activated, to bridge the gap between innate and adaptive.

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19
Q

List some examples of professional antigen presenting cells.

A

Macrophages
B-cells
Dendritic cells

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20
Q

What is MHC? what other term could be used for this?

A

MHC - major histocompatability complex
Also known as Human Leukocyte Antigens (HLA).

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21
Q

What is the structure of MHC 2?

A

Heterodimeric receptor, both sections contribute to binding site
Like a hot dog - is open ended binding site
Binding groove hols longser peptides (13-17 amino acids).

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22
Q

What is the structure of MHC 1?

A

Heterodimeric receptor. one section os shorter, second section expands over the top to make the binding site.
Like a tortilla - the binding site is closed at one end.
Binding groove holds short peptides typically 8-10 amino acids long.

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23
Q

What is the deal with major histocompatability genes?

A

Polygeny - several genes (6 genes 12 alleles)
Polymorphism - variation in a population.

Class 1 MHC loci encode for HLA-A,B and C antigens
Class 2 MHC loci encode for HLA-DP, DQ and DR antigens

Other genes in the MHC region encode for proteins that process antigens.

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24
Q

How does variation in MHC genes have an application?

A

Creates variation is how well an individual is able to present antigens to a cell surface, hence how quickly and effective the adaptive response can be triggered.
Better presenting often have a better experience of disease as immune system is triggers more efficiently.

25
Q

Explain the process of MHC1 presentation?

A

Infection of body cell
Pathogen is chopped up by proteosome
New viral particles are synthesised in the ER
Antigens are loaded onto MHC1 in the endoplasmic reticulum and presented on the membrane by exocytosis.
Activates CD8+ cytotoxic cells.

26
Q

Explain the process of MHC2 presentation?

A

Phagocytosis of the antigen by the antigen presenting cell.
Pathogen is chopped up by phagolysosome
Antigens are loaded onto MHC2 in the phagolysosome.
Presented on the cell surface by exocytosis
Activates CD4+ Helper T Cells.

27
Q

What are the three different signals needed to activate naive t cells?

A

1)T cell receptor binding to the antigen presented by MHC2.
-causes the formation of an immune synapse
2)Co-stimulation CD28/80/86 on T-cell binds to B7 on PAPC
3)Cytokines are produced by the PAPC that instruct the T-cell to become the correct type of effector cell.

28
Q

What are the different sub types of helper T cells?

A

1
2
17
FH
reg

29
Q

What are the features of T-helper 1 cell?

A

IL-12 release from APC triggers development
by transcription factor T-bet.

Produces IFNy cytokines to activate macrophages.

30
Q

What are the features of T-helper 2 cell?

A

IL-4 release from APC to trigger development
by transcription factor GATA3

Produces IL4, 5 and 13 to activate eosinophils, mast cells and macrophages.

31
Q

What are the features of T-helper FH cell?

A

IL 6, 23 and TGFbeta release from APC to trigger development by Bcl6 transcription factor.

Produces IL21 and IL4 to activate and mature B cells.

32
Q

What are the features of T helper 17 cells?

A

IL 6 and 21 are produced by APC to trigger development by RORyT transcription factor

Produces IL 17 and 22, to enhance neutrophil response.

33
Q

What are the features of T helper reg cells?

A

TGFbeta is produced by APC to trigger development by FoxP3 transcription factor.

Produces cytokines IL 10 and TGFbeta to suppress other T cells.

34
Q

What are the two killing mechanisms that a cytoxic T cell uses?

A

Perforin/granzyme
FasL interaction.

35
Q

What is the FasL interaction of killing mechanism in a cytotoxic T cell?

A

FasL ligan on cytotoxic T cell binds to Fas receptor on target cells.
This interaction activates FADD and then pro-caspase 8 in the target cell.
Caspases results is apoptosis.

36
Q

What is the perofin/granzyme kill mechanism of cytotoxic t cells ?

A

Exocytosis of lytic granules at the immune synapse
Attack target membrane by perofin and granzyme from within lytic granules
Perofins polymerise to form pores in the target cell membrane, allows granzymes to enter
Triggers caspase cascade leading to DNA cleavage and death.

37
Q

How does the activation of T helper cells link to the activation of cytotoxic T cells?

A

Both bound to same antigen presenting cell
Activated T helper cell has a CD40 ligand which binds to CD40 receptor on the APC
This enhances APC survival and helps signal to activate CD8+ t cells.
Also causes APC to produce IL 12 to activate more t cells, CD4+ t cell produces IL 2 which binds directly to CD8+ to help activate it.

38
Q

What is meant by cross presentation?

A

When an extracellular antigen taken up by phagocytosis gets presented on the membrane by MHC1 (NOT MHC2) of dendritic PAPC.

39
Q

Give an overview of B-cells?

A

Produced and mature in the bone marrow.
Very high variation and specificity in BCR (B cell receptors) due to recombined antigen receptors
Can differentiate into memory cells or plasma cells which produce antibodies.

40
Q

What is the structure of a B-Cell Receptor (BCR)?

A

Identical to an antibody, two short and two heavy chains cross linked by disulfide bonds, with variable and constant regions
Only difference is receptor also has a transmembrane domain.

41
Q

What do B-cell receptors bind to?
How is this different to T-cell receptors?

A

Directly to antigens even if they are still attached to the pathogen
T-cell Receptors only bind to antigens presented to them by APC.

42
Q

What three signals does a B-cell require to be activated?

A

1)BCR acts as an antigen presenting cell with help of MHC 2, antigen is bound to by CD4+ t cell (follicle helper).
2)Co-stimulation CD40 receptor on B-cell is bound to by CD40L on t cell.
3)Cytokines produces by the T cell instruct the B-cel on what type of antibody to produce.

43
Q

What is the first antibody class to be made?

A

IgM

44
Q

What other term may be used to refer to antibodies?

A

Immunoglobin

45
Q

What makes the different classes of antibody different?

A

Has a different heavy chain constant region.

46
Q

What are the five different types of antibodies and their role?

A

IgM - first made on first encounter with antigen
IgA - secreted a mucosal sites
IgD - binds to basophils
IgE - parasites and allergies
IgG - multi-purpose, high affinity, cross placenta
MADE girls find men being pigs at Morrisons.

47
Q

What is the role of IL-4 in antibody production?

A

Inhibits expression of IgM and IgG3 and IgG2a
Induces expression of IgG1 and IgE

48
Q

What is the role of IL-5 in antibody production?

A

Augments production of IgA.

49
Q

What is the role of IFN-y in antibody production?

A

Inhibits the expression of IgM, IgG1 and IgE
Induces the expression of IgG2b and IgA

50
Q

What is the role of IL-21 in antibody production?

A

Induces the expression of IgG3, IgG1 and IgA.

51
Q

What are the five different antibody functions?

A

1) Neutralisation of toxins - binds to toxins to surround them and prevent binding to host receptor
2)Opsonisation - more tasty for phagocytosis
3) Complement activation - by classical pathway
4)Bind to surface of infected cells and attract NK cells
5)Degranulation of eosinophils and masts, causes basophils to be activated for anti-microbial and anti-inflammatory.

52
Q

What antibodies aid neutralisation?

A

IgA IgG

53
Q

What antibodies aid opsonisation?

A

IgG

54
Q

What antibodies aid complement activation?

A

IgM IgG

55
Q

What antibodies aid NK cell sensitisation?

A

IgG

56
Q

What antibodies aid in activating eosinophils, masts and basophils?

A

Eosinophils - IgE
Mast - IgE
Basophils - IgD.

57
Q

What is the relationship between MHC and HLA?

A

HLA is the human version of an MHC

58
Q

Draw a diagram to show the structure of MHC2 and MHC1?

A
59
Q

What are the professional antigen presenting cells?

A

Macrophages
B cells
Dendritic cells