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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
Give the structural differences between MHC I and MHC II
MHC I - 1 cytoplasmic tail, asymmetrical, (gap at the corner) - CD8 and 4 MHC II - 2 cytoplasmic tails, symmetrical (gap at top) CD4
26
What is HLA
Human leukocyte antigen - genes found in all vertebrates that code for MHC. polygenic
27
Where is HLA found
Chromosome 6
28
What type of expression is HLA
Co-dominant
29
Relationship between HLA and MHC
``` MHC class I = A,B,C MHC class II = DP, DQ, DR ```
30
What is haplotype
Group of MHC alleles on 1 chromosome
31
Describe the endogenous MHC pathway
MHC I. Synthesised in the cytoplasm 1. TAP transports protein to RER 2. calnexin and calreticulin and tapasin fold and stabilise the MHC 4. molecules transport to the golgi
32
Describe the exogenous MHC pathway
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
Why may antibodies be inefficient
``` Pathogens: Can hide within cells Can change antigen shape Can coat the antigen with antibodies Can produce fake antigens ```
34
What are T cells defined by
inputs (STAT) and outputs (cytokines)
35
How do killer T cells induce apoptosis
Granule release - Perforin, granzyme, granulising Fas ligand - binds to Fas receptor on the cell Release of caspases to drive apoptosis
36
What are the activation steps of a naive T cell
1. TCR/CD8 - MHC I Binding 2. CD28 co-receptor activation 3. cytokines from infected cell
37
What is Th1 involved in
Macrophage activation Delayed type hypersensitivity B cell activation Regulation
38
Describe delayed type hypersensitivity
Recruits monocytes | Activates monocytes and macrophages and keeps them at infection site
39
What occurs when the macrophage cannot kill the pathogen e.g. tuberculosis
1. Cytokine release 2. endothelial cells express proteins 3. Monocyte and Th1 migration 4. Th1 activates monocyte and macrophage
40
What is the process of Th1 amplification
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
Give features of Tfh
Activation by dendritic cells Stimulates B cells Generation of isotope-switched antibodies
42
Describe tuberculosis
Ingested by macrophages TB inhibits phagosome -lysosome fusion and lives in macrophages Granuloma formation contains the infection
43
What is the role of Th2
Targets and stimulates eosinophils Trigger in tracheal epithelia Travels from dendritic to naive
44
What CD marker is expressed on naive memory T cells
CDC45RA+
45
What are the two types of memory T cell
Central and effector
46
What CD is expressed on central memory cells
CCR7
47
What are immune checkpoints
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
What is the function of Treg
Regulation of T cells and tolerant of self-antigens | secretes immune-suppressive cytokines and inactivates dendritic cells
49
What is the function of Th17
Interleukin 17, bacterial control and neutrophil recruitment
50
Describe the process of T cell development
Produced in the bone marrow (CD4-CD8-TCR-) In the cortex = CD4+CD8+TCR+ In the medulla = CD4+CD8-TCR+ vice versa
51
Describe selection in the thymus of T cells
Thymocyte can't bind = apoptosis Weak binding = survival (+ve selection) Strong binding = apoptosis (-ve election) Prevents autoimmunity risks
52
what is the largest burden of disease
Acute lung disease
53
What is the purpose of Interferon type 1
Activation of NK
54
What is the purpose of interferon type 2
Produced by T cells pre-inflamamtion
55
Define cytokine storm
Over production of cytokines and accumulation of cells
56
What are the main modes of pathogen transmission
Respiratory - large SA GI tract - large SA Zoonosis Sexually transmitted
57
Describe bacterial defence
``` Surface defence Antibody opsonisation assisted by complement Phagocytosis Inflammatory mediators Fever ```
58
What are the features of an eradicable disease
``` Simple and cheap to diagnose Genetically stable pathogen Accessible host species Eliminated persistent infection Safe and effective vaccine ```
59
What are the features of the ideal vaccine
``` Completely safe easy to administer cheap stable active against all variants life-long protection ```
60
Describe virus defence
``` Surface defence Interferons Inflammatory mediators, acute phase proteins NK cells Antibody and complement T cells ```
61
What is the purpose of immune regulation
Survival of the infected organism Avoid excessive lymphocyte activation and tissue damage Avoid inappropriate reaction against self-antigens
62
Give examples of autoimmune diseases
Hashimoto's | Myasthenia Gravis
63
Define pathologic
Immune response against a self antigen, often classified under immune mediated inflammatory diseases
64
Define pathogenesis
susceptibility genes and environmental triggers
65
Define tolerance
Specific unresponsiveness to an antigen that is induced by exposure of lymphocytes to that antigen
66
What is an allergy
Immune response to non-infectious antigens that cause tissue damage and disease
67
What are allergies mediated by
IgE -> mast cells -> acute anaphylactic shock or T cells (delayed hypersensitivity)
68
Describe hypercytokinaemia
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
What is the 3 signal model
Licensing a response 1. Antigen recognition 2. Co-stimulation 3. Cytokine release
70
How is immune response controlled
Apoptosis of lymphocytes Antigen memory cells survive Responses against pathogens decline as the infection is eliminated
71
Compare central to peripheral tolerance
central - destroys self-reactive T or B cells | peripheral - destroy or control self-reactive cells that do enter circulation
72
What is AIRE
AutoImmune Regulator | A gene for a specialised transcription factor that allows expression of genes in peripheral tissues for self tolerance
73
What is the function of IL-10
``` Master regulator Shuts down dendritic cells Pleitropic (multifunctional) Blocks pro-inflammatory cytokine synthesis Downregulates macrophages ```
74
What are the main mechanisms of peripheral tolerance
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
Which transcription factor does Treg express
FoxP3
76
What are the two types of Treg
Natural Tregs - develops in the thymus | Inducible Treg - Th converted to Treg when exposed to an APC

MCD (13 decks)

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