Immunology 2 Flashcards

1
Q

Are B cells part of the innate or adaptive immune system

A

adaptive immune system

Humoral response

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2
Q

What are immature and mature B cells

A

immature - Not fully developed/differentiated e.g. stem cells
mature - Fully developed and differentiated

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3
Q

What are naive and effector B cells

A

naive - Mature lymphocyte that has not met its antigen

effector - mature lymphocyte that has met its antigen

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4
Q

What is Ig gene rearrangement and where does it occur

A

In the bone marrow
One gene can produce multiple antibodies
Antibodies undergo election to destroy self targets

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5
Q

Which enzyme is involved in Ig gene rearrangement

A

VDJ recombinase

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6
Q

What are the 2 activation pathways when B cell meets antigen

A

T cell dependent

T cell independent

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7
Q

Where does specificity of the B cell come from

A

BCR

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8
Q

Which immunoglobulin classes are present on naive B cells int the blood

A

IgM and IgD

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9
Q

Describe the BCR

A

B cell receptor
Surface bound antibody that represents the the cell produces
Made up of Ig-alpha and Ig-beta
Each chain is encoded by separate multigenerational families

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10
Q

What is MHC I and where is it found

A

Found on all nucleated cells

Indicates the health of the cell by protein presentation

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11
Q

What is MHC II

A

Found on all APC

  • dendritic
  • macrophages
  • B cells
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12
Q

Describe the process of T cell dependent B cell activation

A
  1. Phagocytosis of the pathogen
  2. Pathogen broken down and displayed on the B cell and the dendritic cell via MHC II
  3. T helper recognises the presented antigen on the dendritic cell then finds the B cell with the same antigen
  4. Co-stimulatory molecules (CD28) provides more signalling
  5. T cells produce cytokines
  6. Lymphokine secretion
  7. B cell enters the cell cycle and produces clones with identical BCR
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13
Q

What does class switching involve

A
IgM and IgD are "weak"
When signals (lymphokines) are given from T helper there is a class switch
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14
Q

Where does affinity maturation occur

A

Germinal centres

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15
Q

Describe the process of affinity maturation

A

AID enzyme causes a mutation in the antibody coding genes of the B cells (somatic hypermutation)
Cells can become worse -> apoptosis
Cells can become better -> stronger antibodies -> plasma or memory cell

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16
Q

Explain clonal selection

A

From a large population, 1 cell is activated via antigen binding to BCR which leads to proliferation (clonal selection). Division and differentiation is clonal expansion

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17
Q

What are the advantages and disadvantages of B cells

A

Major vaccine targets
Monoclonal antibody use e.g. cancer, asthma, pregnancy testing, viral infection

Negative role in autoimmune conditions e.g. myasthenia graves
Involved in allergies and cancers

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18
Q

Describe the T cell independent activation pathway

A

A repetitive bacterial polysaccharide acts as the first signal
Microbial constituent or accessory cell provides second signal e.g. LPS

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19
Q

What causes differences in Ig for T cell independent and dependent

A

No lymphokines released in T cell independent

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20
Q

Describe the TCR

A

The Fab region of an antibody, top is variable, bottom is constant. One alpha and one beta and a cytoplasmic tail.

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21
Q

What proportion of T cells have an alpha and beta chain what what do the rest of the T cells have

A

95% T cells

Others are gamma and delta

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22
Q

What is the difference between the alpha and beta chains of the TCR

A
alpha = V and D and 1 recombination
Beta = V, D and J and 2 recombinations
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23
Q

What molecules are found on the T cell membrane

A

CD3
Zeta proteins
TCR

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24
Q

What are CD4 and CD8 and where are they found

A

Co-receptors that bind to MHC.

CD4 is found one T helper cells while CD8 is found on T cytotoxic cells

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25
Q

Give the structural differences between MHC I and MHC II

A

MHC I - 1 cytoplasmic tail, asymmetrical, (gap at the corner) - CD8 and 4
MHC II - 2 cytoplasmic tails, symmetrical (gap at top) CD4

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26
Q

What is HLA

A

Human leukocyte antigen - genes found in all vertebrates that code for MHC. polygenic

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27
Q

Where is HLA found

A

Chromosome 6

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28
Q

What type of expression is HLA

A

Co-dominant

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29
Q

Relationship between HLA and MHC

A
MHC class I = A,B,C
MHC class II = DP, DQ, DR
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30
Q

What is haplotype

A

Group of MHC alleles on 1 chromosome

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31
Q

Describe the endogenous MHC pathway

A

MHC I. Synthesised in the cytoplasm

  1. TAP transports protein to RER
  2. calnexin and calreticulin and tapasin fold and stabilise the MHC
  3. molecules transport to the golgi
32
Q

Describe the exogenous MHC pathway

A

MHC II. Antigens from external environment

  1. invariant chain stabilised the MHC complex
  2. transport to the golgi
  3. invariant chain is digested to leave a CLIP
  4. Antigen is endocytose and broken down
  5. Peptide presented on MHC
  6. MHC exocytosed
33
Q

Why may antibodies be inefficient

A
Pathogens:
Can hide within cells
Can change antigen shape
Can coat the antigen with antibodies
Can produce fake antigens
34
Q

What are T cells defined by

A

inputs (STAT) and outputs (cytokines)

35
Q

How do killer T cells induce apoptosis

A

Granule release - Perforin, granzyme, granulising
Fas ligand - binds to Fas receptor on the cell
Release of caspases to drive apoptosis

36
Q

What are the activation steps of a naive T cell

A
  1. TCR/CD8 - MHC I Binding
  2. CD28 co-receptor activation
  3. cytokines from infected cell
37
Q

What is Th1 involved in

A

Macrophage activation
Delayed type hypersensitivity
B cell activation
Regulation

38
Q

Describe delayed type hypersensitivity

A

Recruits monocytes

Activates monocytes and macrophages and keeps them at infection site

39
Q

What occurs when the macrophage cannot kill the pathogen e.g. tuberculosis

A
  1. Cytokine release
  2. endothelial cells express proteins
  3. Monocyte and Th1 migration
  4. Th1 activates monocyte and macrophage
40
Q

What is the process of Th1 amplification

A
  1. Activated Th1 binds to MHC II and CD40 on the B cell
  2. Secretion of IFN gamma
  3. Upregulation of MHC II, CD40 and tumour necrosis factor alpha
  4. Increase in TNF alpha secretion (autocrine) from macrophages
  5. amplification
41
Q

Give features of Tfh

A

Activation by dendritic cells
Stimulates B cells
Generation of isotope-switched antibodies

42
Q

Describe tuberculosis

A

Ingested by macrophages
TB inhibits phagosome -lysosome fusion and lives in macrophages
Granuloma formation contains the infection

43
Q

What is the role of Th2

A

Targets and stimulates eosinophils
Trigger in tracheal epithelia
Travels from dendritic to naive

44
Q

What CD marker is expressed on naive memory T cells

A

CDC45RA+

45
Q

What are the two types of memory T cell

A

Central and effector

46
Q

What CD is expressed on central memory cells

A

CCR7

47
Q

What are immune checkpoints

A

Expressed on T cells after a large number of exposures (co-stimulatory receptors) causes a longer time for response
T cell quality deteriorates after a long time and proliferation decreases as the number of exposures increase
(different to B cells which undergoes affinity maturation and Ig switching)

48
Q

What is the function of Treg

A

Regulation of T cells and tolerant of self-antigens

secretes immune-suppressive cytokines and inactivates dendritic cells

49
Q

What is the function of Th17

A

Interleukin 17, bacterial control and neutrophil recruitment

50
Q

Describe the process of T cell development

A

Produced in the bone marrow (CD4-CD8-TCR-)
In the cortex = CD4+CD8+TCR+
In the medulla = CD4+CD8-TCR+ vice versa

51
Q

Describe selection in the thymus of T cells

A

Thymocyte can’t bind = apoptosis
Weak binding = survival (+ve selection)
Strong binding = apoptosis (-ve election)
Prevents autoimmunity risks

52
Q

what is the largest burden of disease

A

Acute lung disease

53
Q

What is the purpose of Interferon type 1

A

Activation of NK

54
Q

What is the purpose of interferon type 2

A

Produced by T cells pre-inflamamtion

55
Q

Define cytokine storm

A

Over production of cytokines and accumulation of cells

56
Q

What are the main modes of pathogen transmission

A

Respiratory - large SA
GI tract - large SA
Zoonosis
Sexually transmitted

57
Q

Describe bacterial defence

A
Surface defence
Antibody opsonisation assisted by complement
Phagocytosis
Inflammatory mediators
Fever
58
Q

What are the features of an eradicable disease

A
Simple and cheap to diagnose
Genetically stable pathogen
Accessible host species
Eliminated persistent infection
Safe and effective vaccine
59
Q

What are the features of the ideal vaccine

A
Completely safe
easy to administer
cheap
stable 
active against all variants
life-long protection
60
Q

Describe virus defence

A
Surface defence
Interferons
Inflammatory mediators, acute phase proteins
NK cells
Antibody and complement
T cells
61
Q

What is the purpose of immune regulation

A

Survival of the infected organism
Avoid excessive lymphocyte activation and tissue damage
Avoid inappropriate reaction against self-antigens

62
Q

Give examples of autoimmune diseases

A

Hashimoto’s

Myasthenia Gravis

63
Q

Define pathologic

A

Immune response against a self antigen, often classified under immune mediated inflammatory diseases

64
Q

Define pathogenesis

A

susceptibility genes and environmental triggers

65
Q

Define tolerance

A

Specific unresponsiveness to an antigen that is induced by exposure of lymphocytes to that antigen

66
Q

What is an allergy

A

Immune response to non-infectious antigens that cause tissue damage and disease

67
Q

What are allergies mediated by

A

IgE -> mast cells -> acute anaphylactic shock or T cells (delayed hypersensitivity)

68
Q

Describe hypercytokinaemia

A

Too much immune response
positive feedback loop
pathogens enter the wrong compartment e.g. the blood (Sepsis) or failure to regulate response to the correct level

69
Q

What is the 3 signal model

A

Licensing a response

  1. Antigen recognition
  2. Co-stimulation
  3. Cytokine release
70
Q

How is immune response controlled

A

Apoptosis of lymphocytes
Antigen memory cells survive
Responses against pathogens decline as the infection is eliminated

71
Q

Compare central to peripheral tolerance

A

central - destroys self-reactive T or B cells

peripheral - destroy or control self-reactive cells that do enter circulation

72
Q

What is AIRE

A

AutoImmune Regulator

A gene for a specialised transcription factor that allows expression of genes in peripheral tissues for self tolerance

73
Q

What is the function of IL-10

A
Master regulator
Shuts down dendritic cells
Pleitropic (multifunctional)
Blocks pro-inflammatory cytokine synthesis 
Downregulates macrophages
74
Q

What are the main mechanisms of peripheral tolerance

A

Anergy - APC presents the antigen but the T cell is shut down
Deletion - apoptosis of the T cell
Ignorance - less APCs
Regulation - regulation of the response by cytokines from Treg

75
Q

Which transcription factor does Treg express

A

FoxP3

76
Q

What are the two types of Treg

A

Natural Tregs - develops in the thymus

Inducible Treg - Th converted to Treg when exposed to an APC