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Immunology Y5 > Immunology 1 - The immune response to infection/ primary immune deficiencies part 1 > Flashcards

Immunology 1 - The immune response to infection/ primary immune deficiencies part 1 Flashcards

Incomplete - excludes basics and material that is mentioned in subsequent lectures

1
Q

How is pus formed?

What about abscess formation?

A

Following phagocytosis, neutrophils die

When they die, they release residual enzymes which causes the liquefication of closely adjacent material

This forms pus

*8abscess formation: if you get extensive localised formation of pus**

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2
Q

Recall 2 functions of CD4+ T lymphocytes

A

Provide help for development of:

  1. Full B cell response
  2. Some CD8+ T cell responses
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3
Q

Which type of plasma cell is dependent on CD4+ T cells for activation?

A

IgG

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4
Q

Which components of complement comprise the classical pathway?

A

C1 C2 C4

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5
Q

Which components of complement comprise the mannose binding lectin pathway?

A

c4 and c2

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6
Q

What is the role of the membrane attack complex formed at the end of the complement pathway?

A

Makes holes in membranes

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7
Q

What is the first class of immunoglobulin to be made in the adaptive immune response?

A

IgM

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8
Q

What is the difference between oxidative and non-oxidative killing?

A

Oxidative: uses NADPH and hydrochlorous acid
Non-oxidative: uses lysozyme and lactoferrin

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9
Q

Which form of HLA is recognised by CD4 cells?

A

HLA-2

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10
Q

Which form of HLA is recognised by CD8 cells?

A

HLA-1

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11
Q

Which cytokines induce development of CD4 T cells into Th1 cells?

A

IL12 and IFN gamma

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12
Q

What is the function of Th1 cells?

A

‘Help’ CD8 T cell and macropage responses

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13
Q

Which cytokines induce development of CD4 T cells into Th17 cells?

A

IL6 and TGF beta

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14
Q

What is the function of Th17 cells?

A

‘Help’ neutrophil recruitment and enhance generation of autoantibodies

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15
Q

Which cytokine induces development of CD4 T cells into Treg cells?

A

TGF beta

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16
Q

Which cytokine induces development of CD4 T cells into follicular T helper cells?

A

IL6

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17
Q

Which type of T cell produces CD25 and FOXP3?

A

T reg cells

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18
Q

By what mechanism do CD8 cells effect their cytotoxicity?

A

Injection of perforin, which enables granzyme entry
OR
Fas ligand expression

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19
Q

Which cytokines are secreted by CD8 T cells?

A

IFN gamma and TNF alpha

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20
Q

How do CD4 cells activate B cells?

A

Express CD40 ligand, which interacts with CD40 on immature B cell surface, causing the B cell to differentiate

**the ligand is what is needed to activate the recetor; T cell is what is needed to activate the B cell; ligand is on the T cell and the receptor is on the B cell**

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21
Q

Recall the 2 processes that B cells undergo to become mature

A
  1. Class switching
  2. Somatic hypermutation
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22
Q

Which part of an immunoglobulin determines its class?

A

Heavy chain

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23
Q

Which class of immunoglobin forms a pentamer?

A

IgM

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24
Q

Which class of immunoglobulin forms a dimer?

A

IgA

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25
Q

Which portion of an immunoglobulin mediates pathogen identification?

A

Fab portion

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26
Q

Which portion of an immunoglobulin mediates activation of complement/ NK cells?

A

Fc portion

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27
Q

Where is complement produced?

A

Liver

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28
Q

Neutrophils and macrophages:

a) site of production
b) mechanisms of action COMMON to both

A

a) produced in the bone marrow (macrophages - called macrophages once in tissue)
b) mechanism of action
- receptors for: pathogens themselves (via pattern recognition receptors), cytokines/chemokines (detect inflammation), immune complexes (via Fc receptor)
- phagocytic killing: oxidative and non-oxidative

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29
Q

How do neutrophils kill pathogens?

A

Oxidative and non-oxidatvie killing

Release:

  • preformed myeloperoxidase
  • neurtophil elastase
  • defensins
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30
Q

Difference between monocytes and macrophages

A

Monocytes- produced in bone marrow

When they migrate to tissues they are called macrophages

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31
Q

What is the main difference in function between neutrophils and macrophages?

A

Macrophages can present antigen on their surface following phagocytosis, but neutrophils cannot

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32
Q

Which cell surface marker is associated with macrophages?

A

CD14

Recognises LPS on bacterial cell walls

33
Q

Give two examples of pattern recognition receptor

A

Toll like receptor
Mannose receptor

34
Q

Mode of action of NK cells

A
  • inhibitory receptors: recognise self HLA/MHC I
  • activatory receptors: recognise heparan sulfate proteoglycans
  • Loss of inhibitory signals/increase in activatory signals–>activates NK cells
  • NK cells kill altered self cells - ie virus infected or malignant
  • They also secrete cytokines - regulates inflammation and promotes dendirtic cell activity

NB: NK cells are lymphocytes

35
Q

What type of cell is a dendritic cell?

Describe the changes that occurs in dendritic cells following phagocytosis

A

Dendritic cells mediate the transition between innate and adaptive immunity.

After phagocytosis:

  1. Upregulate expression of HLA-1
  2. Express costimulatory molecules
  3. Migrate via lymphatics to lymph nodes (mediated by CCR7)
  4. Process non-self antigen and present it to T cells in lymph nodes to prime the adaptive immune response
36
Q
A
37
Q
A
38
Q

What are the two types of dendritic cells?

A

Immature: detecting pathogens and phagocytosis

Mature: processing pathogens and presenting to T cells

39
Q

How do antigens and lymphocytes reach the lymph nodes from respecive sites?

A

Antigens: reach lymph nodes via migration through lymphatics from the infected site

Lymphocytes: reach the lymph nodes via the blood

After this, lymphocytes and lymph return to the blood via the thoracic duct

40
Q

What are the soluble components of the innate immune system?

A
  1. complement
  2. acute phase proteins
  3. ferritin
41
Q

What are acute phase proteins?

A

Proteins secreted by the liver in response to infection

Examples:

  • IL1/IL6 - pyrogenic
  • CRP - binds to surface of infected cells–> activates the complement cascade via c1q
  • ferritin
42
Q

What is opsonisation?

A

Modification of a pathogen to attract it to a NK or phagocytic cell

May be mediated by antibodies, complement components or acute phase proteins

Enables phagocytosis

43
Q

Summary: which cells of the immune system are phagocytic?

A

monocytes and macrophages

granulocytes

dendritic cells

i.e. NK cells are not phagocytic !!

44
Q

Describe the process of T cell development: overview

A
  1. T cells start as stem cells in bone marrow
  2. Lymphoid progenesis
  3. Pre-T cells go out into circulation
  4. T cells mature in thymus
  5. T cells proliferate
  6. T cells undergo positive and negative selection within thymus
  7. Mature T cells exported to periphery, reside in secondary lymphoid organs
45
Q

Describe the process of maturation of T cells once in Thymus

A
  • TCR with intermediate affinity for HLA moelcules are selected, whilst those with too low or too high affinity are deleted
  • These intermediate affinity T cells undergo further differentiation based on whether they have affinity for HLA class 2 or HLA class 1
    • Those that bind to HLA class II differentiate into CD4 positvie T cells
    • Those that bind to HLA class I differentiate into CD8 positive T ccells
46
Q

CD8+ vs CD4+ T cells

A
  • CD8+ t cells: detect INTRACELLUAR peptides presented by MHC class I (on APC)
    • particularly important for viral infections/malignancy
  • CD4+ t cells: detect EXTRACELLULAR peptides presented by MHC class II (on APC)
    • variety of functions including activation of B cells and development of other T cells
47
Q

Examples of HLA class I and HLA class II molecules

A

HLA class 1: HLA A, HLA B, HLA C

HLA Class II: HLA-DP, HLA-DQ, HLA-DR

**these are expressed on the APC

** they present processed peptide to T cells

48
Q

Summary of different CD4+ T cell subsets

A
49
Q

Function of TH17 cells

A
  • Fungal and bacterial infections
  • Helps neutrophil recruitment
  • Enhance generation of autoantibodies
50
Q

Function of Treg cells

A
  • Secrete IL-10
    • → inhibit the immune response
  • T regs express CTLA-4 on cell surface
    • → directly inhibit T cell activation
51
Q

Function of Follicular helper T cells

A
  • Promotes germinal centre reactions
  • stimulates differentiation of B cells → IgG (memory B cells) and IgA secreting plasma cells
52
Q

Explain the process of B cell maturation

A

Early IgM response

  • they are produced in the bone marrow
  • they leave the bone marrow as PRO B CELLS or PRE B CELLS
  • once they are in the peirpheries they become IgM B cells
  • so when they recognise antigen they are in the IgM state
  • once they recognise antigen, they differentiate into IgM secreting plasma cells

Germinal centre reaction: Somatic hypermutation and istotype switching

  • IgM secreting plasma cells migrate from the peripheries to the lymph nodes
  • Here they encounter CD4+ helper T cells that have previously been primed (in the peripheries) by dendirtic cells (by detection of the SAME antigen)
  • This interaction requires CD40L (T cell) - CD40 (B cell) interaction
  • IgM producing B cells undergo SOMATIC HYPERMUTATION (the receptor mutates to become high affinity) and class switching (IgM switches to IgG, IgE or IgA)
  • Now you have HIGH AFFINITY, IgG/IgA/IgG secreting plasma cells and memory cells leaving the lymph nodes to enter the circulation
53
Q

Structure of antibodies

A
  • two heavy chains
  • two light chains
  • FaB portion: light chain + variable region of heavy chain
  • Fc portion: cosntant region of heavy chain

Fab: recognises antigen

Fc: effector function; interacts with other components of immune system (complement, phagocytes, NK cells)

54
Q

Function of IgA

A
  • protection of mucosal surfaces via salivary, respiratory, gastrointestinal and lacrimal secretions
  • blocks pathogenic ligands from binding to epithelial cell surface receptors
  • IgA is also present in breast milk
    • providing passive immunity in neonates
55
Q

Which antibody is present in breast milk?

A

IgA

*think it’s SECRETORY

56
Q

FUnction of IgD

A
  • found on the cell surface of immature B cells
  • IgD provide role in lymphocyte activation
57
Q

Function of IgG

A
  • the most abundant/ common antibody
  • and occurs in monomer form in the circulation
  • Subclasses of IgG perform different functions,
  • IgG2- fighting encapsulated bacteria
  • IgG also has a role in activating complement proteins

**crosses the placenta

58
Q

Function of IgM

A
  • occurs as a pentamer
  • and has a role in the primary response against pathogens
59
Q

Function of IgE

A
  • is produced in response to parasitic infections,
  • as well as during type I hypersensitivity reactions
  • where it is involved in mast cell activation.
60
Q

Difference in B cells between primary and secondary immune response

A

Primary immune response: early IgM response

Secondary immune response: high affinity IgG and memory cell response

61
Q

Main difference between IgM and IgG plasma cells

A

IgM plasma cells: not dependent on T cell help for generation

IgG: dependent on T cell help

62
Q

Is the complement system part of innae or adaptive immune response?

A

Neither - it just complements the two systems

63
Q

Explain the process of complement activation

A
64
Q

What activates the classical complement pathway?

A

Immune complexes

Hence it requires activation of the adaptive immune response

So it does not occur early

*C1 activates C4 and C2

65
Q

What activates the MBL pathway of complement activation?

A
  • Activated by the direct binding of MBL to microbial cell surface carbohydrates
  • This directly stimulates the classical pathway involving C4 and C2 (but NOT C1)
  • This is NOT dependent on the adaptive immune response
66
Q

How does the alternative pathway of complement activation work?

A

This is directly triggered by binding of C3 to bacterial cell wall components

E.g. lipopolysaccharide of Gram-negative bacteria

E.g. teichoic acid of Gram-positive bacteria

67
Q

What are the main regulatory factors for the alternative pathway?

A

Factor H

C1 inhibitor

–> prevent the alternative pathway from going into overdrive

68
Q

What is the main amplification step of final common pathway?

A

Activation of C3 convertase

Triggers formation of Membrane attack complex via C5-c9

69
Q

Function of MAC

A
  • attacks membranes
  • makes holes in membranes
  • and lyses them
    • → cell death
70
Q

Functions of the complement system

A
  • Increase vascular permeability and cell trafficking to sites of inflammation
  • Opsonisation of immune complexes keeps them soluble
  • Opsonisation of pathogens to promote phagocytosis
  • pathogens are chemically modified
  • Activation of phagocytes
  • Promotes mast cells/ basophil degranulation
  • Punches holes in bacterial membranes
71
Q

Examples of chemokines

A

CCL19 and CCL21 are ligands for CCR7 on dendritic cells

important in directing dendritic cell trafficking to lymph nodes

72
Q

What is VDJ recombination

A

VDJ recombination is the process by which T cells and B cells:

  • randomly assemble different gene segments
  • and nucleic acids are randomly deleted/ added at the sites of rearrangement

Consequence of VDJ recombination:

  • Potential to create vast array of specificities (10^11- 10^12 receptors)
  • Generates unique antigen receptors that can collectively recognise many different types of molecule
  • Auto-reactive cells are likely to be generated
    • Mechanisms must exist to delete or tolerise these autoreactive cells
73
Q

Primary and secondary lymphoid organs

A

Primary:

Bone marrow

Thymus

Secondary

SIte of interaction between naive lmphocytes and microorganisms

Examples: spleen, lymph nodes, MALT

74
Q

What are the constitutive barriers to infection?

A
75
Q
A
76
Q

What markers are expressed by T memory cells vs naive T cells?

A

Naive T cells: CD45 RA

Memory T cells: CD45 RO

77
Q

What is the difference between central and effector memory T cells?

A
78
Q

Describe B cell memory

A

Immunology Y5 (11 decks)

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