Immunology - Introduction Flashcards

1
Q

what barriers does the skin have to infection?

A
  • tightly packed keratinsed cells
  • physiological factors (low pH, low oxygen tension)
  • sebaceous glands (hyrophobic oil repel water/micobes, lysozyme destroys cell walls, ammonia has anti-bac properties)
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2
Q

what barriers does the mucosal surface have to infection?

A
  • secreted mucous (physical barrier, secretory IgA which prevents attachment into epithelia, lysozyme, lactoferrin starves bacteria of iron)
  • cilia (trap and remove pathogens)
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3
Q

what does the commensal bacteria barrier do?

A
  • compete for resoures

- produce fatty acids and bactericidins to inhibit growth

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4
Q

what are the different cells of the innate immune system?

A
  • polymorphonuclear cells (neutrophils, eosinophils, basophils)
  • monocytes and macrophages
  • NK cells
  • dendritic cells
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5
Q

what are the soluble components of the innate immune system?

A
  • complement
  • acute phase proteins
  • cytokines and chemokines
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6
Q

what are the features of the cells of the innate immune system?

A
  • identical in all individuals
  • cells express receptors that allow them to detect and home to sites of infection
  • express PRR to detect pathogens at site of infection
  • phagocytic capacity to engulf pathogen
  • secrete cytokines and chemokines to regulate immune response
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7
Q

where are polymorphonuclear cells produced and where do they go?

A
  • produced in bone marrow

- migrate rapidly to site of infection

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8
Q

what do polymorphonuclear cells express?

A
  • receptors for cytokines and chemokines to detect inflammation
  • PRR to detect pathogens
  • express Fc receptors for Ig (to detect immune complexes)
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9
Q

what do polymorphonuclear cells do?

A
  • capable of phagocytosis/ oxidative and non-oxidative killing (esp neutrophils)
  • release enzymes, histamine, lipid mediators of inflammation from granules
  • secrete cytokines and chemokines to regulate inflammation
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10
Q

where are mononuclear cells present?

A

monocytes produced in bone marrow
circulate in blood to migrate to tissues
differentiate into macrophages

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11
Q

what do mononuclear cells do?

A
  • capable of phagocytosis/ oxidative and non-oxidative killing (esp neutrophils)
  • secrete cytokines and chemokines to regulate inflammation
  • present processed antigen to T cells
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12
Q

what are macrophages called in the liver?

A

Kupffer cells

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13
Q

what are macrophages called in the kidney?

A

mesangial cells

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14
Q

what are macrophages called in the bone?

A

osteoclast

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15
Q

what are macrophages called in the spleen?

A

sinusoidal lining cell

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16
Q

what are macrophages called in the lung?

A

alveolar macrophage

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17
Q

what are macrophages called in the neural tissue?

A

microglia

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18
Q

what are macrophages called in the connective tissue?

A

histiocyte

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19
Q

what are macrophages called in the skin?

A

langerhans cells

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20
Q

what are macrophages called in the joints?

A

macrophage like synoviocytes

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21
Q

how are phagocytes recruited?

A
  1. cellular damage and bacterial products = local production of cytokines and chemokines
  2. cytokines activate vascular endothelium = enhanced vascular permeability
  3. chemokines attract phagoyctes
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22
Q

how are microorganisms recognised?

A
  • PRRs recognise PAMPs

- Fc receptors bind to Fc portion of Ig to allow for recognition

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23
Q

what is the purpose of opsonisation?

A
  • facilitates endocytosis

- opsonins act as a bridge between pathogen and phagocyte receptor

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24
Q

what are the 2 microbial killing mechanisms?

A
  1. oxidative killing

2. non oxidative killing

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25
Q

what are the steps to oxidative killing?

A
  1. NADPH oxidase converts oxygen to oxygen radical
  2. superoxide dismutase converts radical to hydrogen peroxide
  3. myeloperoxidase converts this with Cl- to hydrochlorus acid (HCOl)
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26
Q

what happens in non-oxidative killing?

A
  • release of lysozyme and lactoferrin into phagolysosome

- enzymes present in distinct specific granules

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27
Q

describe the formation of pus

A
  • phagocytosis depletes neutrophils glycogen reserves
  • neutrophil death
  • as cell dies, enzymes release and liquify local tissues
  • accumulation of dead/dying neutrophils = pus
28
Q

where are NK cells present?

A

within blood and migrate to inflamed tissues

kills altered self or virus infected

29
Q

what do NK cells express?

A
  • inhibitory receptors for self-HLA molecules to prevent mal activation by normal self
  • a range of activator receptors
30
Q

what is the function of NK cells?

A
  • integrate signals from inhibitoru and activator receptors

- secrete cytokines to regulate inflammation (promote dendritic cell function)

31
Q

where do you find dendritic cells? what do they represent?

A

reside in peripheral tissues

represent innate-adaptive transition

32
Q

what to dendritic cells express? purpose?

A
  • cytokine/chemokine receptors to detect inflammation
  • PRRs to detect pathogens
  • Fc receptors for Ig to detect immune complexes
33
Q

what are the functions of dendritic cells?

A
  • capable of phagocytosis (following this the DC mature)
  • upregulate expression of HLA molecules
  • express costimulatory molecules
  • migrate via lymphatics to lymph nodes (mediated by CCR7)
  • present processed antigen to T cells in lymph nodes to prime adaptive response
  • express cytokines to regulate immune response
34
Q

what are the components of the adaptive immune system?

A
  • humoral immunity (B lymphocytes, antibodies)
  • cellular immunity (T lymphocytes = CD4, CD8)
  • soluble components (cytokines and chemokines)
35
Q

what are the characteristics of the adaptive immune response?

A
  • wide repertoire of antigen receptors
  • good specificity (detects small difference in molecule structure)
  • clonal expansion (appropriate cells will proliferate during infection)
  • immunological memory
36
Q

what are the primary lymphoid organs and what do they do?

A

organs involved in lymphocyte development

  • bone marrow: T and B cells derived, B cells mature
  • thymus: T cells mature
37
Q

what are secondary lymphoid organs and what do they do?

A

sites of interaction between naive cells and microorganisms

  • spleen
  • lymph nodes
  • MALT
38
Q

describe the process of T lymphocyte maturation?

A
  • arise from haematopoetic stem cells
  • exported as immature cells to thymus
  • undergo selection
  • mature T lymphocytes enter circulation and reside in secondary lymphoid organs
39
Q

what do CD8+ T cells recognise?

A

recognise peptides presented by HLA class I molecules

40
Q

what do CD4+ T cells recognise?

A

recognise peptides presented by HLA class 2 II molecules

41
Q

how does selection and central tolerance of T cells work?

A
  • low affinity for HLA (not selected to avoid inadequate reactivity)
  • intermediate affinity for HLA (positive selection, around 10% of cells)
  • high affinity for HLA (negative selection to avoid autoreactivity)
42
Q

what decides how T cells differentiate?

A
  • intermediate affinity for HLA class I = differentiate as CD8+ T cell
  • intermediate affinity for HLA class II = differentiate as CD4+ T cell
43
Q

what are the 3 different types of T lymphocytes?

A
  • CD4+ Helper cells
  • CD8+ Cytotoxic Killer cells
  • T cell memory
44
Q

what do CD4+ Helper cells do?

A
  • recognise peptides presented on HLA class 2 molecules
  • immunoregulatory functions via cell-cell interactions and expression of cytokines
  • provide help for developing full B cell response
  • provide help for developing some CD8+ T cell response
45
Q

what do CD8+ cytotoxic cells do?

A
  • specialised cytotoxic cells that kill cells directly (perforin and granzymes, expression of Fas ligand)
  • recognise peptides derived from intracellular proteins (from HLA class 1)
  • secrete cytokines
  • important in defence against viruses and tumours
46
Q

wgat do T memory cells do?

A
  • response to successive exposures to antigen is quicker and bigger than first exposure
47
Q

what are the CD4+ T cell subsets?

A
Th1
Th17
Treg
TFh
Th2
48
Q

what do Th1 cells do?

A

help CD8 T cells and macrophages

secrete IFN gamma, IL-2, IFN alpha, IL10

49
Q

what do Th17 cells do?

A

help neutrophil recruitment
enhance generation of autoanitbodies
secrete IL-17

50
Q

what do T reg cells do?

A

express Foxp3 and CD25

IL-10/TGF beta expressing

51
Q

what do T follicular helper cells do?

A

promote germinal centre reactions and differentiation of B cells into IgG and IgA secreting cells

52
Q

what do Th2 cells do?

A

secrete IL4, IL5, IL13, IL10
allergy (IL-4)
helper T cells

53
Q

how does central tolerance work in B cells?

A
  • no recognition of self in bone marrow = survive

- recognition of self in bone marrow = negative selection to avoid autoreactivity

54
Q

describe the steps to B lymphocyte activation?

A
  • B cell receptor binds to antigen
  • some B cells mature to plasma cells (secrete IgM)
  • if signalled from CD4+ T cells, B cells rapidly proliferate
55
Q

what happens to B cells to improve specificity?

A
  • isotype switching to IgG, IgA, IgE (needs CD40)

- somatic hypermutation to generate high affinity receptors

56
Q

what part of the immunoglobin determines the antibody class?

A

heavy chain

57
Q

what is the function of antibodies?

A
  • identify pathogens/toxins

- interact with other components of immune response (complement, phagocytes, NK cells)

58
Q

what are the features of the secondary immune response (B cell memory)?

A
  • lag time between antigen exposure to antibody production is decreased
  • more antibodies produced
  • response dominated by IgG antibodies of high affinity
  • may be independent of help from CD4+ lymphocytes
59
Q

what is the complement system?

A

> 20 proteins
produced in liver
present as inactive molecules in circulation
when triggered, enzymatically activate each other in biological cascade

60
Q

what are the 3 pathways in which complement can be activated?

A
  1. classical pathway
  2. mannose binding lectin
  3. alternative pathway
61
Q

describe the classical pathway

A

antibody + C1 –> C2, C4 –> C3
changed antibody site exposes C1 binding site
C1 binding to antibody activates cascade
antibody-antigen immune complexes

62
Q

describe the mannose binding lectin pathway

A

MBL –> C2, C4 –> C3
binding of MBL to microbial cell surface CHO
direct stimulation of classical pathway
not dependent on acquired immune response

63
Q

describe the alternative pathway

A

PAMP –> C3
C3 binds to bacterial cell wall components (e.g. LPS)
involves factors B, I, P
not dependent on acquired immune response

64
Q

which is the major amplification step in the complement cascade?

A

C3

65
Q

what happens when complement is activated?

A
  • inc vascular permeability and cell movement
  • opsonisation of immune complexes
  • opsonisation of pathogens (promote phagocytosis)
  • active phagocytes
  • promote mast cell and basophil degranulation
  • form MAC (via C5-C9) to punch holes in membrane