Immunology Flashcards

1
Q

What are the 2 types of immune response in mammals?

A

Acquired and innate

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2
Q

What are the 2 types of acquired immunity?

A

T and B cell

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3
Q

What are the 3 types of innate immunity?

A
  • Complement cascade
  • Phagocytes
  • Physical barriers
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4
Q

Name the innate immunity mammalian leukocytes (5)

A
  • Neutrophil
  • Eosinophil
  • Basophil
  • NK cells
  • Mast cells
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5
Q

Name the antigen presenting cells (4)

A
  • Monocyte
  • Macrophage
  • B lymphocytes
  • Dendritic cells
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6
Q

What is the relationship between plasma cells and B cells?

A

Plasma cells are differentiated B cells

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7
Q

What is the relationship between monocytes and macrophages?

A

Macrophages differentiate from monocytes once they are in tissues. Monocytes are found in blood

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8
Q

What are the 3 pathways of complement activation?

A
  • Classical
  • Lectin
  • Alternative
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9
Q

What are the outcomes of complement activation?

A
  • Altered membranes allowing bacterial lysis and opsonisation
  • Opsonisation facilitates phagocytosis of the pathogen
  • Inflammation leading to, and caused by, mast cell degranulation and neutrophil chemotaxis, which also causes pathogen destruction
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10
Q

How does the complement activation lead to inflammation?

A

Stimulation of histamine release from mast cells (mast cell degranulation)

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11
Q

How does the complement system lead to direct bacterial lysis?

A

Pore formation in cell membranes by Membrane Attack Complexes (formed by complement components)

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12
Q

What is the activating signal for the classical complement pathway?

A

Antigen:Antibody complex

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13
Q

Which complement proteins are anaphylatoxins?

A

C3a, C4a, C5a

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14
Q

What effects to anaphylatoxins have on the body?

A
  • Contraction of smooth muscle
  • Increased vasodilation in local blood vessels increasing movement within tissues and lymph flow
  • Activates mast cells or neutrophils
  • Increases fluid in tissue and speeds up lymph flow
  • Increases chemotaxis
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15
Q

Outline the development of acute inflammation at mucosal surfaces

A
  • Epithelium damaged due to breach by pathogen
  • Leads to cytokine production and chemokine release from epithelial cells (ECs)
  • Stimulates resident cells e.g. mast cells
  • Recruits innate immune cells
  • Histamine and other vasoactive substances increase vascular permeability from mast cells
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16
Q

What is the effect of neutrohphils on inflammation?

A

Increases inflammation, are pro-inflammatory

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17
Q

What are the results of acute inflammation?

A
  • Increased vascular permeability

- Recruitment of cells and diapedesis

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18
Q

Where are acute phase proteins/reactants produced?

A

In the liver

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19
Q

What stimulates the production of acute phase proteins/reactants?

A

Cytokines secreted during inflammation IL-6 and IL-1, TNFalpha)

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20
Q

What acute phase proteins are secreted in response to IL-6?

A

C-reactive protein (CRP) and fibrinogen

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21
Q

What acute phase proteins are secreted in response to IL-1 and/or TNFalpha?

A

Serum amyloid A protein

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22
Q

What is the clinical significance of acute phase proteins?

A
  • Can be markers for systemic inflammatory response
  • Determine severity of disease
  • Can be used to monitor the response to treatment
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23
Q

Name the pro-inflammatory cytokines

A
  • TNFalpha
  • IL-1
  • IL-6
  • CXC-8/IL-8
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24
Q

Name the anti-inflammatory cytokines

A
  • IL-4

- IL-10

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25
Q

What are the effects of pro-inflammatory cytokines

A

Recruit cells to area for inflammatory response

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26
Q

What are the effects of anti-inflammatory cytokines?

A
  • Promote production of antibody
  • Mops up pathogen and reduces inflammatory response
  • Adaptive response present, more specific and will resolve disease faster
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27
Q

What factors determine the immunity to pathogens?

A
  • Intracellular vs extracellular pathogen
  • Innate and adaptive immune responses
  • Ig isotype location and function
  • Complement, opsonisation, phagocytosis and removal of pathogen
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28
Q

Give the events leading to immunological memory

A
  • Pathogen/antigen invasion
  • Ag capture and processing, Ag recognition
  • Selection of lymphocytes specific for that antigen
  • Cell activation
  • Proliferation of antigen specific lymphocytes to form a clone
  • Differentiation into a function (effector) state or memory state
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29
Q

What is the function of antigen tolerance?

A

Prevents damage to self and regulates immune response to environmental antigens and fetus during pregnancy

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30
Q

What are the types of antigen tolerance?

A
  • Central

- Peripheral

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31
Q

Where and when does central antigen tolerance develop?

A
  • Education of T lymphocytes in thymus
  • B lymphocytes in bone marrow
  • Occurs during maturation
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32
Q

Where and when does peripheral antigen tolerance develop?

A
  • T and B cells in secondary lymphoid tissue

- Occurs after birth

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33
Q

What is hypersensitivity?

A

Sensitisation as a result of repeated exposure of genetically susceptible individuals to the same antigen

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34
Q

What are the types of hypersensitivity?

A
  • Type I: antibody mediated, immediate
  • Type II: antibody mediated, cytotoxic activity, days
  • Type III: immune complex mediated, 24h
  • Type IV: cell mediated, delayed type (DTH), 24-72h
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35
Q

Give examples Type I hypersensitivities

A
  • Localised: atopic dermatitis, flea allergy dermatitis, sweet itch, allergic rhinitis, asthma, food
  • Systemic: bee stings, penicillin
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36
Q

Give examples of Type II hypersensitivityes

A
  • Incompatible blood transfusion e.g. in cats

- Autoimmune disease: haemolytic anaemia, thrombocytopaenia, neutropaenia, myasthenia gravis

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37
Q

Give examples of Type III hypersentivities

A
  • Allergy to fungal spores in cattle
  • Recurrent airway obstruction in horses
  • Blue eye in dogs
  • Leishmaniosis in dogs
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38
Q

Outline Type III hypersensitivity

A
  • Ab excess or Ag excess
  • Immune complexes (Ag - Ab) form
  • Deposit in wall of small capillaries (e.g. renal glomerulus, uveal tract, synovoium, cutaneous epidermal basement membrane)
  • Can lead to vasculitis and ischaemia necrosis
39
Q

Give examples of causes of Type IV hypersensitivities

A
  • Environmental allergy e.g. pemphigus foliaceus (Mycobacterium spp. response)
  • Above forms the TB test for cattle
40
Q

Outline the development of a Type IV hypersensitivity response

A
  • Th cells reactivated on re-exposure to an Ag they have been sensitised to
  • Release IFNy and chemokines
  • HEVs form
  • Upregulation of vascular adressins
  • Recruitment of mononuclear cells
  • Become walled off
41
Q

Outline the development of a granuloma in chronic inflammation

A
  • Granulomas are aggregates of chronically stimulates inflammatory cells
  • Collection of macrophages modified to form epithelioid cells with surrounding zone of T lymphocytes
  • Macrophages fuse to form Langhans giant cells
  • Centre becomes caseous and necrotic, eventually undergoes fibrosis and calcification
42
Q

What methods can be used to test for antibodies?

A
  • Latex agglutination
  • Serology (to detect infection, seroconversion)
  • ELISA
  • Coomb’s test
  • Radial immunodiffusion
  • ANA
  • Paired serology testing for respiratory disease diagnosis
43
Q

What are the 2 types of immunodeficiency?

A
  • Primary (young animals)

- Secondary (adults)

44
Q

What is an important clinical consequence of immunodeficiency regarding?

A

May reduce or prevent entirely, vaccination effectiveness

45
Q

Outline the importance of T and B lymphocytes in veterinary medicine

A
  • Diagnostics and herd health monitoring
  • Rational design of vaccines
  • Immune mediated disease
  • Immunodeficiencies
  • Tolerance e.g. to food antigens
  • Immunosuppression
  • Pharmacological control of inflammation
  • Cancer e.g. leukaemia or lymphoma diagnosis and prognosis
46
Q

What is primary lymphoid tissue?

A

The tissue in which lymphocytes are generated/matured

47
Q

Name the primary lymphoid tissues

A
  • Bone marrow
  • Thymus gland
  • Bursa of Fabricius (birds)
  • Ileal patches (sheep, cattle, pigs, dogs, horses)
  • Appendix caecal patch (rabbits)
48
Q

What is secondary lymphoid tissue?

A

Where lymphocytes interact with APCs and immune responses are generated. Is where antigens are presented to naive lymphocytes

49
Q

Name the secondary lymphoid tissues

A
  • Lymph nodes
  • MALT
  • BALT
  • Spleen
50
Q

Outline lymphocyte recirculation

A
  • Naive lymphocytes recirculate through blood and lymph continuously until meet specific Ag in LN
  • Stimulates cell activation, division, lymph node enlarges, activated lymphocytes leave LN in lymph
  • Enter blood via thoracic duct then into tissues at site of infection
  • Formation of memory cells, leave blood when encounter specific Ag again
51
Q

What are the subsets of T lymphocytes?

A
  • CD4+ Th
  • CD8+ Tc
  • Treg
52
Q

Briefly describe cytotoxic T lymphocytes

A
  • CD8+
  • MHC class I restricted
  • Kill cells infected with intracellular pathogens
53
Q

Briefly describe helper T lymphocytes

A
  • CD4+
  • MHC II restricted
  • Th1, Th2 and Th17 subsets
54
Q

Briefly describe the role of Th1 lymphocytes

A
  • Proinflammatory

- Activate cytotoxic T lymphocytes to kill intracellular pathogens

55
Q

Briefly describe the role of Th2 lymphocytes

A
  • Anti-inflammatory

- Stimulate B cells’ antibody production and class switchin

56
Q

What are the Th1 cytokines?

A
  • Proinflammatory

- IFNy and TNFa mainly

57
Q

What is the role of the Th1 cytokines?

A

Activate macrophages and mediate delayed type hypersensitivity

58
Q

What are the Th2 cytokines?

A
  • IL4

- IL5

59
Q

What is the role of the Th2 cytokines?

A

Promote differentiation of B cells into antibody secreting plasma cells

60
Q

Briefly describe the role of Th17 lymphocytes

A
  • Secrete IL-17

- Neutrophil recruitment, fungal infection and autoimmunity

61
Q

Briefly describe regulatory T lymphocytes

A
  • CD25+, FoxP3 +

- Release Il-10 and TGFb

62
Q

What is the role of Tregs?

A
  • Regulate immune response

- Crucial in tolerance development

63
Q

What is the clinical relevance of the different subsets of lymphocytes?

A
  • Pathogens vary in how they are present to immune system (extra vs intracellular)
  • Type of immune response generated differs
  • for some pathogens, Th1 bias cellular immunity, for others Th2
64
Q

What is the main difference between T cell receptors and B cell receptors?

A
  • T cell receptors will only recognise antigen if present to them on MHC class I or II molecules on other cells
  • B cell receptors can bind to antigens directly (can be bound to cell or free in plasma)
65
Q

What allows T cell receptors to recognise a diversity of antigens?

A
  • T cell receptors highly diverse and unique to cell type

- Due to genetic changes that lead to alterations in structure

66
Q

What is CD3?

A

T cell receptor

67
Q

What part of the antigen to TCRs recognise?

A

Small peptide fragment

68
Q

Describe the genetic changes that take place to allow the diversity in T cell receptors

A
  • Somatic DNA recombination of different gene segments of V (variable) region
  • V domain encoded by 3 gene segments
  • V encodes first 95 amino acids, D encodes 5 amino acids, J encodes last 10-15 amino acids
69
Q

What cells carry MHC class II?

A

Selected cells, mainly APCs

70
Q

What cells carry MHC class I?

A

Nearly all nucleated cells in the body

71
Q

Why is MHC class I present on most cells?

A

So virtually any cell can present peptide antigens to CTLs

72
Q

What type of antigen processing is carried out by MHC class I?

A

Endogenous

73
Q

What type of antigen processing is carried out by MHC class II?

A

Exogenous

74
Q

Outline what happens following recognition of an antigen on an MHC I/II molecule by a CTL/Th cell

A
  • Engagement between CTL’s TCR and CD8 molecules OR Th’s TCR and CD4 molecules
  • In both cases, additional molecular binding (second signals) secure interaction and ensure activation of lymphocyte
75
Q

What is processed by exogenous processing for antigen presentation?

A
  • Infectious agents present in extracellular spaces
  • Environmental agents e.g. pollen, dust mites, food
  • Opsonised agents, B cell receptor bound
76
Q

Outline the process of exogenous antigen processing and presentation

A
  • Antigen enters host cell via phagocytosis and pinocytosis, in endosomes
  • Large proteins of antigen broken into smaller proteins suitable for presenting to T cells
  • Peptides bind with MHC class II before being taken to cell surface where endosome fuses with cell membrane
77
Q

How are exogenous antigens processed by APCs?

A
  • Pattern Recognition Receptors (PRRs) recognise PAMPs on microorganisms, bind to B cell receptors on B cells
  • Phagocytosis and processing follows
78
Q

What MHC class carries out exogenous antigen processing and presentation?

A

MHC class II

79
Q

What MHC class carries out endogenous antigen processing and presentation?

A

MHC class I

80
Q

What is processed by endogenous antigen processing?

A
  • Antigens of self
  • Tumour antigens
  • Intracellular virus antigens
  • Parasitic antigens
  • i.e. anything intracellular
81
Q

Outline the process of endogenous antigen processing and presentation

A
  • Antigen enter cytoplasm
  • Tagged with ubiquitin
  • Enters proteasome
  • Proteins degraded into peptides
  • Transproted to endoplasmic reticulum where associate with MHC class I
  • Complex moves through Golgi to be expressed on cell surface
82
Q

What is the importance of cross presentation of antigens?

A
  • Need mixed response to an antigen, not just CTL or antibody response
  • However some allergens/pathogens may have a bias towards one or the other
83
Q

What determines the bias of an allergen/pathogen immune response?

A

The route of antigen uptake i.e. more endogenous uptake leads to more CTL response

84
Q

What is the clinical importance of the route of antigen processing and presentation?

A

Affects the method by which a vaccine or adjuvant needs to work. E.g. if an antigen is predominantly processed exogenously, a vaccine where the primary route of processing is endogenous will offer some protection but will not allow full protection against that pathogen when protected naturally

85
Q

What is the function of plasma cells?

A

Secretion of antibodies

86
Q

What do B cells differentiate into?

A

Lymphoblasts and plasma cells

87
Q

What are the roles of B cells?

A
  • Differentiation into lymphoblasts and plasma cells
  • Proliferation of B cells
  • APCs to MHC class II restricted Th cells
88
Q

What stimulates the proliferation of B cells?

A

Binding of antigens to B cell receptors bound to the surface of the cell, allowing binding of Th cells which then release cytokines that promote division and activation of B cells

89
Q

Outline the process of clonal expansion of lymphocytes

A
  • Once antigen is presented, co-stimulation occurs
  • Costimulation depends on cell type
  • Lymphocyte activated then divides
  • Multiple clones of identical antigen specific lymphocyte are produced
90
Q

What occurs if an antigen is presented but the co-stimulation signal cascade is absent/incomplete?

A

Tolerance to the antigen. This may be beneficial or deleterious

91
Q

What is immunodeficiency?

A

Immune system is damaged and unresponsive. May be genetic and is non-specific

92
Q

What is the difference between immunodeficiency and antigen tolerance?

A

Immunodeficiency is non-specific whereas tolerance is antigen specific

93
Q

Describe the changes that occur within cells during clonal expansion following antigen binding and co-stimulation

A
  • Cell enlarges (lymphoblast)
  • Lymphoblasts divide
  • IL-2 secreted by T cells, promoting proliferation
  • Effector and memory cells produced