Partridge (Immune System) Flashcards

1
Q

What is immunology?

A
  • study of immune system
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2
Q

What is immune system?

A
  • integrated system of cells and molecules that defend against disease, by reacting against infections
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3
Q

What is the medical importance of immunology?

A
  • vaccination
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4
Q

Examples of malfunctions in immune system?

A
  • immunodeficiency
  • allergy
  • autoimmune disease
  • graft rejection
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5
Q

What are immunological techniques?

A
  • research, diagnostics, therapeutics
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6
Q

How do bacteria carry out immune surveillance?

A
  • restriction enzymes
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7
Q

How do invertebrates carry out immune surveillance?

A
  • negative surveillance, cells marked w/ “self” protein labs, unlabelled non-self cells destroyed by phagocytes
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8
Q

How do vertebrates carry out immune surveillance?

A
  • external barriers (skin)
  • negative surveillance by major histocompatibility complexes, v polymorphic
  • positive surveillance specific recognition of foreign cells (active immunity)
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9
Q

What is the difference between innate and adaptive immune system?

A
  • innate has broad specificity and adaptive highly specific
  • in innate resistance resistance not improved by repeat infection, but is in adaptive
  • innate has rapid response (hrs) and adaptive has slower response (days-wks)
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10
Q

What does 2º contact w/ antigen result in?

A
  • enhanced adaptive responses
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11
Q

What are the external barriers to infection?

A
  • keratinised skin –> keratin difficult for bacteria to digest and must be damaged to infect
  • secretions –> sebum, sweat, FAs, lactic acid, lysosyme = low pH, dry and salty
  • mucous –> cilia in resp tract traps pathogens
  • low pH of 2.5 in stomach
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12
Q

What is commensalism?

A
  • 1 organism benefits from another
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13
Q

What are the 3 types of phagocytes?

A
  • neutrophils
  • mononuclear phagocytes
  • mast cells
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14
Q

What are the characteristics and role of neutrophils?

A
  • main phagocyte in blood
  • short-lived
  • fast moving
  • lysosomes release enzymes (H2O2) etc.
  • unusual shaped nucleus
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15
Q

What are the characteristics and role of mononuclear phagocytes?

A
  • monocyte in blood/macrophage in tissue
  • long lived (months-yrs)
  • help initiate adaptive responses
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16
Q

What are the characteristics and role of mast cells?

A
  • underlying mucosal surfaces in skin
  • release inflammatory mediators (eg. histamine)
  • important in parasite and allergy response
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17
Q

What are the characteristics of NK cells?

A
  • type of lymphocyte
  • kill virally infected cells non-specifically
  • important in self/non self recognition and may kill cancer cells
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18
Q

How are pathogens recognised by phagocytes/mast cells? (innate)

A
  • have general pathogen recognition receptors (PRRs)
  • that recognise pathogen-assoc molecular pattern (PAMPs)
  • eg. Toll-like receptor 4 recognises LPS
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19
Q

How are pathogens recognised by NK cells? (innate)

A
  • kills target unless they recognise self protein (MHCI)
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20
Q

What are the integrated responses to infection/injury?

A
  • inflammation (v beneficial), localised response to infection and damage (dilation of blood vessels, increase in capillary permeability, phagocytes migrate into tissue)
  • PAMPS/DAMPS (pathogen/damage assoc mol pattern)
  • induces release of inflammatory mediator and prod of cytokines
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21
Q

3 examples of soluble factors

A
  • complement system
  • defensins
  • interferons
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22
Q

What is the complement system?

A
  • approx 20 proteins in blood
  • activated on infection
  • bacterial cell lysis
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23
Q

What are defensins?

A
  • positively charged peptides
  • made by neutrophils
  • disrupt bacterial membranes
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24
Q

What are interferons?

A
  • prod by virally infected cells
  • protect uninfected cells
  • activate macrophages and NK cells
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25
What are soluble factors also involved in?
- cell to cell communication
26
What are cytokines?
- 'hormones of immune response' - eg. interleukins (act between WBCs) - prod by cells of innate and adaptive IS
27
Example of inflammatory mediator?
- histamine
28
How is temp response (fever) an example of an acute phase response?
- on infection, macrophages may release interleukin 1 (IL-1) - acts on hypothalamus - increases temp - stimulates phagocytosis - decreases Fe levels in blood
29
How are antigens recognised by adaptive IS?
- by specific receptors on T and B lymphocytes
30
Where do B and T lymphocytes mature and then move to?
- B mature in bone marrow - T mature in thymus - move to central lymphoid tissue (antigen independent differentiation)
31
What occurs during maturation of lymphocytes?
- acquire antigen receptors
32
What is the difference between the receptors of B and T lymphocytes?
- B are antibodies | - T are T cell receptors
33
What type of differentiation occurs in peripheral lymphoid tissue?
- antigen dependent differentiation
34
What is the role of B lymphocytes, type of immunity they provide and infections they work against?
- secrete antibodies - humoral immunity - for extracellular bacterial and 2º viral infection
35
What is the role of T lymphocytes, type of immunity they provide and infections they work against?
- kill infected host cells - make cytokines - cell mediated immunity - for viral, intracellular bacterial and intracellular parasitic
36
What was the role of Jenner in immunology?
- developed vaccination principles - showed infection w/ cowpox protected against smallpox - as shared antigens
37
What does the cell mediated (T cell) immune response involve?
- clonal expansion, differentiation, memory | - T cells can only recognise antigen bound to host cell
38
What is the clonal selection hypothesis?
- millions of B cells prod - when 1 w/ correct antibody binds to antigen, triggers clonal selection of this cell - lymphocytes that recognise "self" deleted early in dev
39
What are the types of vaccine?
- subunit, eg. toxoid (from toxin) | - attenuated strains
40
How is lymphoid tissue organised?
- 1º is where lymphocytes reach maturity | - 2º is where mature lymphocytes stimulated by antigen, clustered around places of entry
41
What is humoral (antibody) immunity?
- antigen --> B lymphocytes (antibody receptor) --> plasma cells --> soluble antibody
42
What class do antibodies belong to?
- class of soluble glycoproteins, called immunoglobulins
43
How does an antibody's structure reflect its dual role in immune response?
- antigen recognition = Fab regions variable in seq and binds diff antigens specifically - antigen elimination = Fc region constant seq, binds to component, Fc receptors on phagocytes and NK cells etc.
44
What is the role of antibodies?
- act as labels for infectious material | - labelled material "eliminated"
45
What do Fab and Fc mean?
- Fab = fragment antigen binding | - Fc = fragment crystallisable
46
How do the sizes vary between the light chain, heavy chain and total molecule?
- L = 25kD - H = 50kD - L2H2 (immunoglobulin G) = 150kD
47
What AA is the hinge range rich in, and why?
- Pro - so flexible - but susceptible to proteolytic digestion
48
What are the 5 immunoglobulin classes of H chain and how do they differ?
- IgG (γ) - IgM (μ) - IgA (α) - IgD (δ) - IgE (ε) - differ in AA seq of H chains
49
What are the 2 types of L chain and are they class restricted?
- kappa (κ) - lambda (λ) - no, can have IgGκ or IgGλ antibodies
50
What is the variable region of an antibody?
- binds antigen | - differ between antibodies w/ diff specificities
51
What is the constant region of an antibody?
- same for all antibodies of given H chain class of L chain type
52
Are the variable and constant regions of an antibody encoded by the same exon?
- no, encoded by separate exons
53
How can multiple variable regions in genome give diff antibody specificities?
- regions can recombine and mutate during B cell differentiation
54
How do H chain classes differ in 2º response?
- can include IgA and IgE - same amount of IgM - much more IgG
55
How do antibodies use specific binding/valency to protect against infection, and what H chain classes do these involve?
- Fab region - neutralise, eg. toxins (IgG, IgA) - immobilise mobile MOs (IgM) - prevent binding to and infection of host cells - form complexes, cross link antigens on diff pathogens to clump them together, so easier to deal w/
56
How do antibodies use effector functions to protect against infection, and what H chain classes do these involve?
- Fc region - activate complement (IgG, IgM) - bind Fc receptors, phagocytes (IgG), mast cells (IgE), NK cells (IgG)
57
What does the complement induce?
- inducer of inflammation, can cause pathology
58
How are serum proteins activated in complement?
- 20 serum proteins activated via enzyme cascade
59
How is the complement activated?
- specifically by antigen/antibody complexes (classical pathway) - or non-specifically, by eg. certain bacteria (MB-lectin or alternative pathway)
60
What are the 3 major biological activities of the complement?
- activation - opsonisation - cell lysis
61
What happens during activation by complement?
- phagocyte recruitment - induces inflammation - C5a (or C3a) - chemoattractants (causes chemotaxis) - anaphylatoxins (mast cells release lots of inflammatory mediators all over body)
62
What happens during opsonisation by complement?
- C3b binding and phagocytosis - C3b binds to bacterium membrane - phagocytes have receptors, so can be bound w/ high affinity and destroyed more efficiently
63
What happens during cell lysis by complement?
- need activation of whole cascade | - membrane attack complex: C9 --> polymers --> hollow cylinders which form pores in bacterial membranes
64
What is involved in the classical pathway? (complement)
- req Ag/Ab2, C1, C2, C4 - 2 IgG molecules attached to bacterial cell surface - C1 must interact w/ 2 Fc regions - IgM more potent activator of complement (pentamer)
65
What is the role of Fc receptors on phagocytes?
- IgG and IgA most important - some classes of antibodies can act as opsonins - pseudopods fuse to form phagosome and release contents - phagolysosome acid, peptides, toxic O derivatives, competitor enzymes
66
What is the role of Fc receptors on NK cells?
- only IgG has receptors on NK cells - mediate antibody dependent cell-mediated cytotoxicity (ADCC) - secrete perforin from granules, allows passage of particles to induce apoptosis - target undergoes apoptosis, cell contents destroyed and "corpse" taken up by macrophages
67
What is the role of Fc receptors on mast cells?
- IgE - mediate allergy and defence against large particles - allergen binds to specific IgE, causing degranulation, which releases inflammatory mediators, eg. histamine, causing local inflammation - beneficial in response to particles
68
What is an epitope?
- antibodies of similar structure
69
How is antisera production used in research and medicine?
- conventional antisera = polyclonal antisera - used to give 2º response (IgG in animals) - remove small amount of blood and allow to clot - may lack fine specificity and difficult to standardise
70
How are monoclonal antibodies used in research and medicine?
- single specificity (binds 1 epitope) - derived from single B lymphocyte - B cells from animal immunised w/ antigen A and isolated - B cells fused w/ tumour cell line (divide indefinitely) - prod hybrid cells, make anti-A antibody
71
How are antibodies used in research, diagnostics and therapy?
- identifying and labelling molecules in complex mixtures - serotyping pathogens - characterising cell surface proteins, identifying cell types - "humanised" antibodies, used in therapy, magic bullets to kill cancer cells
72
What are the 2 major sub pops of T cells and what are their roles?
- T helper cells --> help B cells make antibodies, activate macrophages and Nk cells, help dev of cytotoxic T cells - T cytotoxic cells --> recognise and kill infected host cells
73
What is the structure of T lymphocyte receptor (TCR) and how does this relate to its function?
- v similar to Fab arm of antibody | - variable regions responsible for antigen recognition
74
What do B and T cells recognise?
- B recognise "soluble" free native antigens - T recognise "cell-assoc" processed antigens - cytotoxic T cells recognise peptide bound to MHCI
75
What happens during T cell recognition of antigen?
- viral proteins in a virus infected cell broken down in cytosol (proteasomes) - peptides transported to ER, bind MHCI w/ cell surface - activated cytotoxic T cells kill infected cell by inducing apoptosis - helper T cells recognise protein bound to MHCII - macrophage/dendritic cell/B cell internalises and breaks down foreign material - peptides bind to MHCII in endosomes on cell surface - activated T helper cells help B cells make antibody and prod cytokines that activate/reg other leucocytes
76
What is the problem w/ lymphocytes meeting antigen?
- lymphocyte w/ specific receptor must meet antigen
77
What is lymph?
- extracellular fluid that accum in tissues and carried by lymphatic vessels back through lymphatic system to thoracic duct and into blood
78
Where is adaptive immunity activated?
- in draining lymph node
79
What encodes major histocompatibility proteins?
- major histocompatibility gene complex (MHC) | - chromosome 6
80
What is the role of major histocompatibility proteins?
- initiating T cell responses | - important in graft rejection
81
Are major histocompatibility proteins polymorphic, and what does this mean?
- yes, v polymorphic - most polymorphic proteins in man - many diff alleles at each gene locus
82
Where are major histocompatibility proteins expressed?
- MHCI on all nucleated cells, displays antigen to CD8+ve (cytotoxic T cells) - MHCII on macrophages, dendritic cells and B cells, displays antigen to CD4+ve (helper T cells)
83
What are cytokines and what is their role?
- small (approx 5-20kD) secreted proteins - involved in communication between cells of immune response - can have autocrine or paracrine activity - usually prod and act locally - act by binding to specific receptors on target cell surface
84
What are the main groups on cytokines and their roles?
- interleukins (IL-1 - IL-38?) --> usually made by T cells - interferons (IFNs) --> viral infections, cell activation - chemokines --> cell movement or chemotaxis - colony stimulating factors (CSFs) --> leucocyte prod
85
What cytokines do diff types of T helper cells prod?
- TH1 cells --> inflammatory intracellular infections, prod IL-2, γ-interferon and TNFβ - TH2 cells (parasitic) --> prod range of interleukins - TREGs, suppress other T cells
86
How does HIV infect cell?
- 2 copies ss RNA enter cyto - RNA to DNA by reverse transcriptase - takes part of host cell as it leaves, creating envelope, gp120 = viral receptor - virus binds to cell receptor - virus envelope fuses w/ plasma membrane - nucleocapsid enters cyto - viral RNA reverse transcribed into ds DNA - viral DNA transported to nucleus and integrated into host cell genome (provirus) - new viral genomic RNA and mRNA transported to cyto - viral mRNA translated to viral protein - new nucleocapsids form and virus "buds" from cell - acquires lipid envelope
87
Which cells and how many are infected by HIV?
- CD4+ve cells susceptible to infection - no. T cells infected increases w/ each round of viral rep - monocytes, macrophages and dendritic cells also infected, as low levels CD4+ve
88
How does latent HIV infection progress?
- T cell stimulation activates HIV provirus transcrip | - T cell lysis
89
How do dendritic cells and monocytes respond to HIV infection?
- dendritic cells present antigen to T cells in lymphoid tissue - monocytes may traverse blood/brain barrier, CNS involvement
90
How can CD4 expression affect HIV infection?
- not sufficient for HIV infection - but may influence susceptibility to infection/disease progression - progression slower if young and healthy - some not susceptible as no chemokines
91
What are the co-receptors for the HIV virus?
- chemokine receptors
92
How do symptoms of HIV progress to AIDS?
- 'flu-like' symptoms - (seroconversion occurs) - asymptomatic - symptomatic - AIDS - death
93
What is the immune response to HIV?
- high levels of virus in blood initially cleared (mainly by cytotoxic T cells) - antibodies may not be detected for 3-6 months (seroconversion) --> B may not be helped by T helper cells - IS mounts vigorous response against virus, CD8+ve cytotoxic T cells esp important
94
How does HIV avoid immune detection?
- mutates
95
What does T helper cell depletion lead to immune response against HIV?
- direct lysis by virus - killed by cytotoxic T cells or other immune mechanisms - infected cells in lymphoid tissue
96
What are the symptoms of AIDS?
- opportunistic infections, eg. Candida - reactivation of latent infections - rare cancers (caused by viruses) - CNS involvement, dementia - all adaptive immune response compromised
97
What do the symptoms of AIDS show about T helper cells and how?
- that they're vital in IS | - as memory T cells lost
98
What are the differences between HIV-1 and HIV-2?
- HIV-2 slower to progress to AIDS | - HIV- 2 predates HIV-1
99
How is HIV transmitted?
- unprotected sex (approx 70%) - blood/blood products (mainly IV drug use, approx 28%) - breast feeding - mother to foetus
100
How can HIV/AIDS be prevented through changes in behaviour?
- blood testing - safe sex - decrease in IV drug use/needle sharing - treating HIV +ve pregnant women
101
What are the problems with preventing HIV/AIDS through vaccination?
- difficult due to high mutation rate - humoral immunity may not be productive - need to induce cytotoxic T cells (some people never progress to AIDS due to elite ones)
102
How can HIV/AIDS be prevented through drug therapy and what are the problems?
- problems = high mutation rate, toxicity, viral latency, cost - combo therapy = 3+ drugs directed at diff viral targets - no. infected hasn't decreased much
103
What future treatments could be available for AIDS?
- gene editing - immunisation of infected patients, "kick and kill" - possible immunisation using human monoclonal antibodies