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YEAR 5: Immunopathology > Immuno: Immune response to infection Pt.2 > Flashcards

Immuno: Immune response to infection Pt.2 Flashcards

1
Q

What are the key features of cells of the adaptive immune response?

A
  • Wide repertoir of antigen receptors (NOTE: not entirely genetically encoded because of VDJ recombination)
  • Highly specific
  • Clonal expansion
  • Immunological memory
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2
Q

Outline T cell maturation

A
  • T cells arise from hematopoietic stem cells
  • Exported as immature T cells to the thymus where they undergo positive and negative selection
  • Cells with low and high affinity for HLA are deleted
  • Cells with intermediate affinity will survive (10%)
  • Mature T lymphocytes enter the circulation and reside in secondary lymphoid organs
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3
Q

How do T cells recognise HLA/peptide complex?

A
  • T cells express CD3 and T cell receptor
  • T cell receptor recognises peptides presented by HLA molecule on APC
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4
Q

Which class of HLA do CD4 and CD8 cells recognise?

A

CD4 - HLA-II

CD8 - HLA-I

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5
Q

Outline the functions of CD4+ T helper cells.

A
  • Recognise peptides derived from extracellular proteins
  • These peptides are presented on HLA-II (HLA-DP, DQ and DR)
  • Provide help for the development of a full B cell response
  • Provide help for the development of some CD8+ T cell responses
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6
Q

List the subsets of CD4+ T cell.

A
  • Th1
  • Th2
  • Th17
  • Follicular T cell
  • Treg
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7
Q

For each of the following subsets of CD4+ T cell, list their polarising factors and effector factors.

  1. Th1
  2. Th2
  3. Th17
  4. Follicular T cell
  5. Treg
A

Th1

  • Polarising
    • IL-12
    • IFN-gamma
  • Effector
    • IL-2
    • IL-10
    • IFN-gamma
    • TNF-alpha

Th2

  • Polarising
    • IL-4
    • IL-6
  • Effector
    • IL-4
    • IL-5
    • IL-10
    • IL-13

Th17

  • Polarising
    • IL-6
    • TGF-beta
  • Effector
    • IL-17
    • IL-21
    • IL-22

Follicular T cell

  • Polarising
    • IL-6
    • IL-1b
    • TNF-alpha
  • Effector
    • IL-2
    • IL-10
    • IL-21

Treg

  • Polarising
    • TGF-beta
  • Effector
    • IL-10
    • Foxp3
    • CD25
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8
Q

Describe the function of CD8+ T cells.

A
  • Specialised cytotoxic cells
  • Recognise peptides derived from intracellular proteins presented on HLA class I (A, B and C)
  • Kills cell directly via perforin and granzyme or expression of Fas ligand
    - Perforin destablises cell membrane and also allows granzyme to enter cell
    - Granzyme is a serine protease that activate caspases to trigger apoptosis

NOTE: particularly important against viral infections and tumours

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9
Q

In what form are B cells found in the periphery?

A

IgM B cells

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10
Q

What is the early IgM response of B cells?

A

If the B cell in the periphery engages an antigen it can cause an early IgM response where the cell differentiates into an IgM secreting plasma cell.

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11
Q

What is a germinal centre reaction?

A
  • Dendritic cells present an antigen, thereby priming the CD4+ T helper cells
  • CD4+ T helper cells provide help for B cell differentiation via CD40L: CD40 interaction
  • This causes B cell proliferation
  • They undergo somatic hypermutation and isotype switching (from IgM to IgG/A/E)
  • They will become plasma cells and produce antibodies

NOTE: this process is dependent on CD4+ T helper cells

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12
Q

Which part of an antibody detects antigen and which part is responsible for its effector function?

A
  • Antigen is recognised by the antigen binding region (Fab) which is made up of the variable region of both heavy and light chains
  • Effector function is determined by the constant region (Fc) of the heavy chain
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13
Q

Outline the function of antibodies.

A
  • Identification of pathogens and toxins (Fab-mediated)
  • Interact with other components (complement, phagocytes, NK cells) of immune responses to remove pathogens (Fc-mediated_

NOTE: antibodies are particularly important against bacteria

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14
Q

How is a secondary response to T-dependent antigens different from the primary response?

A
  • Lag time between antigen-exposure and antibody production is decreased (to 2-3 days)
  • Titres of antibody produced is increased
  • Response is dominated by IgG antibodies with high affinity
  • The response is independent of help from CD4+ cells
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15
Q

Describe B cell maturation

A

Stem cells in BM > lymphoid progenitors > Pro B cells > Pre B cells > IgM B cells in periphery

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16
Q

Describe the central tolerance of B cells

A
  • No recognition of self-antigens = survive
  • Recognition of self-antigens in BM = negative selection to avoid autoreactivity
17
Q

What is complement?

A
  • 20 tightly regulated, linked proteins
  • Produced by liver
  • When triggered, enzymatically activate other molecules in a biological cascade
  • Results in rapid, highly amplified response
18
Q

In what form are complement proteins present in the circulation?

A

Inactive molecules

19
Q

Draw a schematic of the complement pathway.

A
20
Q

Outline the classical pathway of complement activation.

A
  • Activated by immune complexes
  • Formation of antibody-antigen complexes results in a conformational change exposing a binding site for C1 on the antibody
  • This binding results in activation of the cascade (this = formation of C3 convertase)

NOTE: this is dependent on antibodies, therefore it requires prior activation of the adaptive immune response (i.e. it does NOT occur very early in the immune response)

21
Q

Outline the mannose binding lectin 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)

NOTE: this is NOT dependent on the adaptive immune response

22
Q

Outline the alternative pathway of complement activation.

A
  • Directly triggered by the binding of C3 to bacterial cell wall components
  • This is NOT dependent on the adaptive immune response (continuously active at low levels)
  • Involves factors B, D and P
23
Q

State an example of bacterial cell wall components that can activate complement in Gram-positive and Gram-negative organisms.

A

Gram-negative: lipopolysaccharide

Gram-positive: teichoic acid

24
Q

What is the major amplification step of the complement cascade?

A

C3 convertase

25
Q

What are the effects of complement fragments that are released during complement activation?

A
  • MAC
  • Opsonisation
  • Chemotaxis
  • Increase vascular permeability (anaphylatoxin)
26
Q

What are the ligands for the CCR7 receptors on dendritic cells?

A
  • CCL19
  • CCL21
  • This interaction is important in directing dendritic cells towards lymph nodes

YEAR 5: Immunopathology (25 decks)

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