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Year 1 Semester 2 > Immunology > Flashcards

Immunology Flashcards

1
Q

What is the innate immune system?

A

The first line of defence against external pathogens. It is not specific

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2
Q

When does innate immune system respond?

A

Immediately - 0-4 hours

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3
Q

When does the early induced response take place?

A

4-96 hours

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4
Q

When does the adaptive immune response take place?

A

> 96 hours

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5
Q

What routes of entry exist for pathogens (mucosal surfaces)?

A
  • Airway - inhaled droplets
  • GI tract - contaminated food or water
  • GU - physical contact
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6
Q

What routes of entry exist for pathogens through external epithelia?

A
  • External surface - physical contact
  • Wounds and abrasions - minor skin abrasions - punctures
  • Insect bites - mosquito, ticks
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7
Q

What barriers to infection are there?

A
  • Mechanical
  • Chemical
  • Microbiological
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8
Q

What are some mechanical barriers?

A
  • Tight junctions between cells prevent access
  • Air and fluid flow across epithelium
  • Movement of mucus by cilia
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9
Q

What are some chemical barriers?

A
  • Fatty acids on skin
  • Enzymes: lysozyme in saliva, sweat and tears
  • Low pH in stomach
  • Antibacterial peptides: defensins (skin and gut) and cryptidins (gut)
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10
Q

What are some microbiological barriers?

A

Normal flora compete for nutrients and attachment (biofilms), and also produce antibacterial substances (colicins)

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11
Q

What happens when pathogens make it across an epithelial barrier?

A

The microorganisms are recognised and ingested by mononuclear phagocytes, or macrophages

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12
Q

What are some bactericidal effects and agents produced by phagocytes?

A
  • Acidification: pH 3-4, bactericidal
  • Toxic oxygen derived products: superoxide, hydrogen peroxide, hydroxyl radical
  • Toxic nitrogen oxides: nitric oxide
  • Peptides: defensins and other cationic proteins
  • Enzymes: lysosyme, acid hydrolases
  • Competitors: lactoferrin, vitamin B12 binding protein
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13
Q

How do natural killer cells work?

A

Due to their interaction with multiple sites on a healthy cell, they are receiving both an activate (kill) signal and an inhibitory (do not kill) signal causing it to do no harm to the healthy cell. When infected, the healthy cells lose their MHC molecules that are involved in the inhibitory signal and so the don’t kill signal is removed leaving only the kill signal causing the infected cell to be killed by the NK cell

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13
Q

How do natural killer cells work?

A

Due to their interaction with multiple sites on a healthy cell, they are receiving both an activate (kill) signal and an inhibitory (do not kill) signal causing it to do no harm to the healthy cell. When infected, the healthy cells lose their MHC molecules that are involved in the inhibitory signal and so the don’t kill signal is removed leaving only the kill signal causing the infected cell to be killed my the NK cell

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14
Q

What is complement?

A
  • Heat liable component of plasma that act in concert with antibodies to kill some bacteria
  • Comprises a large number of distinct plasma proteins
  • Three distinct activation pathways exist that trigger the complement cascade
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15
Q

What are the names of the pathways that trigger the complement cascade?

A
  • Classical pathway
  • Lectin pathway
  • Alternative pathway
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16
Q

What is the classical pathway of the complement cascade?

A

Antibody binds to specific antigen on pathogen surface

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17
Q

What is the lectin pathway of the complement cascade?

A

Mannose-binding protein binds to pathogen surface

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18
Q

What is the alternative pathway of the complement cascade?

A

Pathogen surface creates local environment conductive to complement activation

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19
Q

What is C3b?

A

An opsonin

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20
Q

What is C3a?

A

A peptide mediator of inflammation

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21
Q

What produces antibodies?

A

B cells

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22
Q

What is the origin of B cells

A

Lymphocytes arise from stem cells in bone marrow, and differentiate in the central lymphoid organs, B cells in bone marrow, T cells in thymus. They migrate in bloodstream to peripheral secondary lymphoid organs, lymph nodes, spleen, gut-associated lymphoid tissue (GALT), Peyers patches, tonsils, appendix

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23
Q

What are naive B cells?

A

B cells that have not met antigen

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24
Q

What are the main site of antigen encounter?

A

Peripheral lymphoid tissues

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25
Q

How do recirculating B cells enter back into the bloodstream?

A

By the thoracic duct

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26
Q

What are the key features of the adaptive immune response?

A

Antigen specificity and memory

27
Q

What are some features of the secondary (memory) response of antibodies?

A
  • Faster
  • Can produce more antibodies
  • Does not prevent you from making a response to another antigen
28
Q

What are the two forms antibodies can be expressed as?

A
  • Membrane bound (B cell receptor - BCR)

- Secreted

29
Q

How many antibody specificities does each B cell have?

A

Just one

30
Q

What are the two separate functions that antibodies have?

A
  • Bind to the pathogen that elicited its production

- Recruit other cells and molecules that will lead to clearance or destruction of the pathogen

31
Q

What is the make up of antibodies?

A
  • Four polypeptide chains - two identical heavy chains, two identical light chains
  • The heavy chains are disulfide bonded to each other and each heavy change is also disulfide bonded to a light chain
32
Q

What are the two types of light chain?

A
  • Lambda

- Kappa

33
Q

Which of the two light chain types are humans more likely to have?

A

Kappa - the ratio is 2:1 in favour of kappa

34
Q

Explain the generation of antibody diversity

A
  • Almost any substance can generate an antibody response. Even responses to simple single antigenic determinants are diverse ie can comprise many different antibodies
  • The total number of antibody specificities available in an individual is called the antibody repertoire, and in humans is at least 10 to the power of 11
  • The number of antibody specificities available at any one time is, however, limited to the total number of B cells present
  • How is such diversity generated? Somatic diversification theory suggests that the repertoire is generated from a limited number of V region genes that undergo alteration
  • The sequence of a V region is generated by the somatic recombination of separate gene segments - chromosomal rearrangement
35
Q

What did germline theory suggest?

A

A separate gene existed for each antibody

36
Q

What causes extra variability of antibodies?

A

Junctional diversity

37
Q

What are the 5 classes of antibody?

A
  • IgG
  • IgM
  • IgD
  • IgA
  • IgE
38
Q

Which antibody class is most common?

A

IgG

39
Q

What are some examples of antibody multimers?

A

IgM can be secreted as pentamers, IgA as dimers.

Both involve an additional J chain in this process

40
Q

What does MHC stand for?

A

Major histocompatibility complex

41
Q

What is human MHC called?

A

Human leukocyte antigen (HLA)

42
Q

Describe the development of T cells

A

T cells derive from bone marrow stem cells. T cell precursor cells arrive in thymus and spend up to 7-21 days undergoing differentiation and proliferation into a mature, but antigen naive, phenotype

43
Q

Explain how T cells are educated

A
  • Small double positive thymocytes (CD4 and CD8) initially express low levels of T cell receptor (TcR)
  • Most of these TcRs won’t recognise your own MHC molecule so the T cells die because of a lack of positive selection
  • Those cells that do see your own MHC go on to mature and express high levels of TcR. They then lose either CD4 or CD8 to become single positive cells
  • During this latter stage the T cells also undergo negative selection, to eliminate T cells that see your own MHC with high affinity ie which could become autoreactive T cells
44
Q

What is the difference between antibodies and T cells in terms of recognising antigens?

A
  • Antibodies bind the antigen they were raised against on its own, that is, free in solution, or maybe in a membrane
  • But the TcR only ever recognises an antigen when it is bound by an MHC molecule
45
Q

Describe MHC class I molecules

A
  • Two chains, a heavy chain and a small beta-2-microglobulin
  • Upper surface forms a groove into which small 8-10 amino acid peptides sit
  • Expressed on almost every cell in your body, though at low levels in some (eg CNS)
46
Q

Describe MHC class II molecules

A
  • Two chains, alpha and beta, both membrane bound
  • Upper surface forms groove into which longer peptides, over 20 amino acids sit
  • Expression more limited to specialised antigen presenting cells and immune cells eg macrophages, dendritic cells, B and T cells
47
Q

What class of MHC is recognised by CD8 T cells?

A

MHC class I

48
Q

What class of MHC is recognised by CD4 T cells?

A

MHC class II

49
Q

Where are the peptides that MHC class I picks up mainly derived from?

A

The internal contents of your cells eg cytoplasm and nucleus

50
Q

Where are the peptides that MHC class II picks up mostly derived from?

A

External sources ie outside the cells

51
Q

Where does MHC class I meet peptides?

A

Endoplasmic reticulum

52
Q

Where does MHC class II meet peptides?

A

In endosomes

53
Q

How do cells of the immune system communicate between themselves, and with other non-immune cells?

A
  • Cell-cell contact, signalling through receptor-ligand interactions between membranes of different cells eg MHC and TcR
  • Secretion of soluble factors that initiate responses and signals by binding to specific receptors
  • Cytokines: usually small polypeptides, around 25000 released by cells in response to an activating stimulus
  • Can behave autocrine: affects cell that secretes it. Paracrine: effects on adjacent cells. Endocrine: effects on distant cells
  • Chemokines: a class of cytokine that has chemoattractant properties ie induces cells to migrate towards the source
54
Q

What are interleukins?

A

Cytokines secreted by leukocytes

55
Q

What is the function of interleukin-8?

A
  • Chemotactic factor

- Recruits neutrophils and T cells to site of infection

56
Q

What is the function of interleukin-2?

A
  • Activates T cells

- Proliferation

57
Q

What is the function of interleukin-4?

A
  • Activates B cells

- Switches them to produce IgE therefore important in allergy

58
Q

What is the function of interferon-gamma?

A

-Activates strong cell mediated responses eg CTL

59
Q

What is the function of TNF-alpha?

A

-Activates vascular endothelium and increases vascular permeability

60
Q

What is the function of interleukin 12?

A

-Differentiates CD4 cells

61
Q

What are the two types of CD4 T cells?

A

Th1 and Th2

62
Q

Describe the function of Th1 cells

A

Macrophage activation, B-cell activation and production of opsonizing antibodies such as IgG1

63
Q

Describe the function of Th2 cells

A

General activation of B cells to make antibodies

64
Q

Describe dendritic cells

A
  • Professional antigen presenting cells that sit at the interface between the innate and adaptive immune response
  • Found in most surface epithelia
  • Highly phagocytic, sampling their external environment. Upon stimulation, cease phagocytosis and migrate to lymph nodes
  • Variety of names: Langerhans cells in skin, interdigitating cells, follicular dentritic cell (FDC) and when migrating in circulation also called veiled cells

Year 1 Semester 2 (26 decks)

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