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ZAHRAH IMMUNO > Immuno: Immune response to infection > Flashcards

Immuno: Immune response to infection Flashcards

1
Q

List some features of skin that makes it an effective barrier to infection.

A
  • Consists of tightly-packed keratinised cells
  • Low pH
  • Low oxygen tension
  • Sebaceous glands
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2
Q

What do sebaceous glands produce that has antibacterial effects?

A
  • Hydrophobic oils - repels water and microorganisms
  • Lysozyme - destroys the structural integrity of the bacterial cell wall
  • Ammonia and defensins - anti-bacterial properties
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3
Q

Describe the defensive features of mucosal surfaces.

A
  • Traps invading pathogens
  • Cilia promote the removal of mucus
  • Contains secretory IgA which binds to pathogens and prevents them from attaching to and penetrating epithelial cells
  • Contains lysozyme and other antimicrobial peptides
  • Lactoferrin starves invading bacteria of oxygen
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4
Q

How do commensal bacteria act as a barrier to infection?

A

Competes with pathogenic bacteria and produces various antimicrobial agents

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5
Q

List the cells of the innate immune system.

A
  • Polymorphonuclear cells
  • Monocytes/macrophages
  • NK cells
  • Dendritic cells
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6
Q

List the soluble components of the innate immune system.

A
  • Complement
  • Acute phase proteins
  • Cytokines and chemokines
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7
Q

List some key features of cells of the innate immune system.

A
  • Identical responses in all individuals
  • Cells express genetically-encoded receptors (PRRs) that allow them to detect pathogens at the site of infection
  • Cells have phagocytic capacity
  • Cells secrete mediators (e.g. cytokines/chemokines) that regulate the immune response
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8
Q

Name the resident macrophage in the following tissues/organs:

  1. Liver
  2. Kidney
  3. Bone
  4. Spleen
  5. Neural tissue
  6. Connective tissue
  7. Skin
A
  1. Liver = Kupffer cells
  2. Kidney = Mesangial cells
  3. Bone = Osteoclasts
  4. Spleen = Sinusoidal lining cells
  5. Neural tissue = Microglia
  6. Connective tissue = Histiocytes
  7. Skin = Langerhans cells
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9
Q

How do macrophages differ from polymorphonuclear cells?

A

They can process antigens and present them to T cells

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10
Q

Outline the process of phagocyte recruitment in response to infection.

A
  • Cellular damage and bacterial products trigger the production of inflammatory mediators (cytokines and chemokines)
  • Cytokines enhance vascular permeability
  • Chemokines attract phagocytes (chem = chemistry = attract)
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11
Q

Describe how cells of the innate immune system recognise pathogens.

A
  • Neutrophils mobilised very quickly from BM and migrate to site of infection
  • Pattern-recognition receptors (PRRs) recognise generic motifs called PAMPs (e.g. bacterial sugars, DNA and RNA)
  • Fc receptors on these cells allow binding to the Fc portion of immunoglobulins thereby allowing phagocytosis of immune complexes
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12
Q

What are examples of PRRs?

A
  • Toll-Like Receptors (TLRs)
  • Mannose Receptors
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13
Q

What is opsonisation?

A

The molecular mechanism that uses opsonins to make a molecule (e.g. antigen) more palatable to the phagocyte.

I.e. opsonins act as a bridge between the pathogen and the phagocyte receptors

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14
Q

Which other factors can bind to phagocytes to facilitate phagocytosis?

A
  • Complement components (e.g. by binding to CR1)
  • Acute phase proteins (e.g. CRP)
  • Antibodies
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15
Q

Describe the formation of a phagolysosome

A
  • Pathogen taken up into phagosome
  • Fuses with lysosome
  • Forms phagolysosome

> > Protected compartment in which killing of organism occurs

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16
Q

Describe the reactions involved in oxidative killing of pathogens within phagolysosomes.

A
  • NADPH oxidase converts oxygen into reactive oxygen species (e.g. superoxide and hydrogen peroxide)
  • Myeloperoxidase catalyses the production of hypochlorous acid (from hydrogen peroxide and chloride)
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17
Q

What is non-oxidative killing?

A
  • Killing by the release of bactericidal enzymes (e.g. lactoferrin, lysozyme)
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18
Q

Why do neutrophils die after phagocytosis? What does this form?

A
  • Phagocytosis depletes the glycogen stores of the neutrophil resulting in neutrophil death
  • The accumulation of dying neutrophils forms pus
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19
Q

How do NK cells determine whether to lyse cells or not?

A
  • They have inhibitory receptors which recognise self HLA and they have activating receptors that recognise heparan sulphate proteoglycans
  • The balance of these signals determines the response
  • I.e. if HLA downregulated, activatory signal will become dominant
  • They kill ‘altered self’ cells (e.g. malignancy or virus-infected cells)
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20
Q

Describe the main features of dendritic cells.

A
  • Reside in peripheral tissues
  • Express receptors for cytokines/chemokines
  • Express pathogen recognitiion receptors
  • Express Fc receptors for immunoglobulin
  • Capable of phagocytosis
  • Present processed antigens to T cells in lymph nodes to prime the adaptive immune response
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21
Q

What does a dendritic cell do after phagocytosis?

A
  • Upregulate expression of HLA molecules
  • Express co-stimulatory molecules
  • Migrate via lymphatics to lymph nodes
22
Q

Which receptor is involved in the migration of dendritic cells to lymph nodes?

A

CCR7

23
Q

What is the difference between primary and secondary lymphoid organs?

A
  • Primary - involved in lymphocyte development (bone marrow and thymus)
  • Secondary - anatomical sites of interaction between naïve lymphocytes and microorganisms (e.g. spleen, lymph nodes, MALT)
24
Q

What is a germinal centre?

A

Area within a secondary lymphoid organ where B cells proliferate and undergo affinity maturation and isotype switching

25
Q

What are the components of the adaptive immune response?

A
  • ‘Humoral immunity’ - B lymphocytes and antibodies
  • ‘Cellular immunity’ - T lymphocytes (CD4 and CD8 cells)
  • Soluble components - cytokines and chemokines
26
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
27
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
28
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
29
Q

Which class of HLA do CD4 and CD8 cells recognise?

A

CD4 - HLA-II

CD8 - HLA-I

30
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
31
Q

List the subsets of CD4+ T cell.

A
  • Th1
  • Th2
  • Th17
  • Follicular T cell
  • Treg
32
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
33
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

34
Q

In what form are B cells found in the periphery?

A

IgM B cells

35
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.

36
Q

What happens in the germinal centre when the dendritic cells arive?

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

37
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
38
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

39
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
40
Q

Describe B cell maturation

A

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

41
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
42
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
43
Q

In what form are complement proteins present in the circulation?

A

Inactive molecules

44
Q

Draw a schematic of the complement pathway.

A
45
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)

46
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

47
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
48
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

49
Q

What is the major amplification step of the complement cascade?

A

C3 convertase

50
Q

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

A
  • MAC
  • Opsonisation
  • Chemotaxis
  • Increase vascular permeability (anaphylatoxin)
51
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

ZAHRAH IMMUNO (11 decks)

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