Week 7 - Immunology Flashcards

1
Q

What is haematopoiesis?

A

The process to make cellular elements in the blood

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2
Q

What are transferrins?

A

Iron binding proteins that inhibit growth of certain bacteria by reducing available iron therefore reducing bacteria proliferation

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3
Q

What are interferons?

A

Produced by lymphocytes, macrophages and fibroblasts that have been infected with a virus. Act as chemical messengers instructing neighbouring cells to produce antiviral proteins that interfere with replication. 3 Types: alpha, beta and gamma, making near cells resistant to viral infections and activation of specific immune system

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4
Q

What is a compliment protein?

A

Protein normally found in inactive state in blood plasma and membranes which forms a compliment system
- Enhances specific immunity and punches holes in cell membrane of pathogens

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5
Q

Describe NKs (Natural killer cells )

A
  • Specialised granular lymphocytes
  • Detects effect of pathogen on host cell by detecting lack of host protein or induction of stress proteins
  • Release peforins or bind and inflict direct damage
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6
Q

Describe virus cell invasion in relation to MHC1

A

Viruses turn of protein secretion and expression of MHC1 is reduced so killer T cells can recognise between infected cells and normal cells

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7
Q

Describe Phagocytes

A
  • Recognise pathogens via specific receptors
  • Multi-lobular nucleus
  • Respond to interleukin
  • Differentiate to form macrophages in tissues
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8
Q

What are eosinophils?

A

Basic Granules
Bind to eosin dye
React to neutrophils and kill larger pathogens ie parasitic worms etc via oxidative killing mechanism

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9
Q

Describe dendritic cells

A
  • Found throughout the body
  • Link between inate and adaptive immune system
  • Actively motile, endocytotic, self antigen injection
  • Potent antigen presenting cells - activation of T lymphocytes
  • Present antibody to B-lymphocytes for activation
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10
Q

Describe inflammation in response to a pathogen

A
  • First response to damage
  • Increases blood supply to tissue bringing fluids
  • Mechanisms trap pathogens
  • Vasodilation, increased permeability of blood vessels, migration of cells into tissue to be repaired
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11
Q

Describe histamines

A
  • Released by mast cells in connective tissue and basophil and platelets in response to injury.
  • Attracts neutrophils and macrophages to the site of the injury and induces increase in vasodilation and permeability of blood vessels
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12
Q

Describe prostaglandins

A
  • Lipids released by damages cells and intensify the effect of histamines and the kinins
  • Migration off phagocytes through capillary wall
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13
Q

Describe kinins

A
  • Formed from inactive precursor molecules called kininogens
  • Induce vasodilation
  • Increase permeability to blood and promotes chemotaxis
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14
Q

Describe leukotrienes

A
  • Act as guidance cue for phagocytes
  • Increase permeability of blood vessels and also function in the adherence of phagocytes to pathogens - released by basophils and mast cells
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15
Q

Describe the complement cascade

A
  • Associated with release of histamine attraction of neutrophils
  • Promotion of phagocytosis and direct bacteria destruction
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16
Q

Describe Pus

A

Pus formation continues until infection had been destroyed

  • dispersed by either drainage or absorption
  • Sometimes it does not drain away resulting in an abscess or inflamed spot
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17
Q

Describe a fever

A
  • Increase in body temperature associated with inflammatory response
  • Bacterial toxins increase the body temperature by stimulating cytochrome and interleukin-1
  • Hypothalamic thermoregulatory set point being elevated
  • Enhance activity of interferons and macrophages and inhibit bacterial cells replication
  • Increase in enzyme activity associated with repair
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18
Q

Describe classically activated monocytes

A
  • Defend against bacteria, protozoa and viruses

- Anti-tumour activity

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19
Q

Describe alternatively activated monocytes

A
  • Anti-inflammatory activity

- Regulate wound healing

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20
Q

Describe regulatory macrophages

A
  • Secrete large amounts of interleukin-10
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21
Q

Describe myeloid derived suppressor cells

A
  • Suppress anti tumour immunity
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22
Q

Describe Macrophages

A
  • upon stimulation they can adopt context dependent phenotypes
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23
Q

Describe the innate immune system

A

Physical Barriers
Inflammatory response - histamine release
Complement antimicrobial proteins
Cells - neutrophils, macrophages, eosinophils and natural killer cells

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24
Q

Describe the adaptive immune system

A

Dendritic cells
Antigen
(1) - B-cells, antibodies, bind to antigen, phagocytosis by neutrophils/ macrophages - Humoural Immunity

(2) - T cells - helper = cytokines, helper leukocytes eliminate antigen
- cytotoxic = killing of cells expressing antigen - cellular immunity

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25
Q

Describe T cells

A

Produced in the bone marrow, mature in the thymus

  • Positive and n negative selection of T cells to enzyme so there is no T lymphocyte that can respond to self
  • CD3 epitope present on all
  • Express CD8 or CD4 cell surface proteins
  • CD8 - When activated in secondary lymphoid tissue - spleen/lymph nodes
  • CD4 - Helper T cells - activate CD8 T cells
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26
Q

Describe B cells

A

Produced and matured in the bone marrow

  • Undergo positive selection
  • activated by binding to specific pathogenic epitope
  • differentiate into plasma cells responsible for antibody secretion
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27
Q

Describe cell mediated immunity

A

CD8 T cells differentiate into cytotoxic T cells

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28
Q

Describe antibody mediated immunity

A

Transformation of B cells into plasma cells secreting and synthesising immunoglobulins or antibodies, binding to specific antigens and inactivate

  • target antigens in body fluid and pathogens in body fluid
  • Aided by CD4 T cell derived helper cells
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29
Q

Describe antigens

A

Non self molecular configuration - foreign epitope - may be a single protein or part of a large complex bacteria
Activate the adaptive response - antibody production
- Lymphocytes recognise components of antigens epitopes recognised by B and T lymphocytes

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30
Q

What are antigens two characteristics?

A

Immunogenicity - ability of epitope to activate immune cells
Reactivity - ability to react with receptors of specific immune cells

Full antigens have both characteristics
Partial antigens have only reactivity - can’t induce an immune response

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31
Q

Describe MHC Class 1 complex

A
  • Presents self proteins on the surface of the cells

- MHC1 expressed only on surface of antigen presenting cells

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32
Q

Describe MHC class 2 complex

A

T cells only recognise antigens presented in context on MHC2 achieved through antigen presenting processing

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33
Q

describe Exogenous antigen processing

A
  • Antigen ingested by phagosome/endosome
  • Digested into small peptides
  • Vesicle containing peptides fuses with MHC2 vesicle
  • Binds to MHC2 and is exported via exocytosis to the cell surface
  • MHC2 is presented to the immune system
  • Antigen processing cell migrates around the body to lymphatic tissue - show to T cells to initiate specific immune system
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34
Q

Describe endogenous antigen processing

A
  • Antigens produced within a cell and fragments became associated with MHC1
  • MHC1 complex moves to cell membrane where its displayed as a surface antigen
  • Phagocytes may present many antigens
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35
Q

Describe co stimulation

A
  • More than 20 known co stimulants
  • after T cell presenting antigen has bound
  • without co stimulation and two stage process dendrocyte would be non functional
  • allows temporary attachment of two cells
  • safeguards in recognition and response to self
  • Immune system response is not exponential

Co stimulation medicated by CD4 membrane protein, CD4 T cells secrete cytokines to stimulate killer T cells/ CD8 T cell increases proliferation

36
Q

Describe binding of MHC 2 with antigen to CD4 T cells

A
  • binding activates co stimulant
  • CD4 activates and stimulates activation of CD4 T cells to produce daughter cells
  • activate memory cells
  • activate T helper cells secrete interleukins and cytokines
37
Q

Describe Cytokines role in the immune system

A

Small molecules/ growth hormones associated with inflammatory responses and cell replication ie interleukin2/3 and TGF-B transforming growth factor

38
Q

Describe TGF-B

A

Highly expressed in embryos and neonates, increased concentration decreases scaring so increasing TGF-B induces scarless healing
- Increases survival of damaged cells - BAD

39
Q

Describe interleukin 2 binding

A

Important in activating killer T cells

  • MHC1 proteins identified within cell cytosol and bound In endoplasmic reticulum
  • Binding inactive CD8 T cells binds to MHC1 presenting cell, activating CD8 T cell via co-stimulation with interleukin 2, activated and cytotoxic T cell
40
Q

describe binging of T cell receptors to MHC2

A

MHC2 brings cell close and releases perforins and perforates virus infected cell
- gamma inferno activates macrophages and encourages phagocytosis

41
Q

Describe positive selection of T cells

A

MHC restriction

- Mediated by thyme epithelial cells in cortex

42
Q

Describe negative selection of T cells

A

deletion of auto reactive cells mediated by bone marrow dendritic cells and macrophages
98% of cells undergo apoptosis and don’t become functioning T cells - prevention of auto immune diseases

43
Q

Describe the specific antibodies and their function (5)

A

IgD- receptor on virgin B cells - activates basophils + mast cells
IgM - Aggluntinin - activates complement - immature B cells secreted into blood - early immunity
IgG - Opsonin - activates complement secreted by plasma cheeks and cross placenta to foetus
IgA - secretory - protects mucosa - found in mucus, saliva, tears and breathing milk
IgE - Inflammatory - protection vs helminths - protects against parasitic worms and responsible for allergic reactions

44
Q

Describe B cell response to antigens

A

B cells differentiate into plasma cells to produce antibodies or memory cells
- progenitor B cells in bone marrow, symptomatic recombination of heavy chain becomes precursor B cell - 2nd systematic recombination of lamda or kappa chains therefore unique receptor - usually IgM immature / naive B cells
- immature B cells migrate to peripheral lymphatic system via afferent lymphatic tissue and migrate to cortex
Activation of interleukins encourages proliferation and differentiation

45
Q

What are antibodies function (6)

A
  • Neutralisation
  • Agglutination
  • Precipitation
  • Complement fixation
  • Optonisation
  • Activation of NK cells

After binding of antibody to antigen conformational change occurs allowing binding of Fc receptors in NK cells which de granulate and kill pathogens

46
Q

What are the two complement activation pathways?

A
  • Lectin pathway

- Alternative pathway

47
Q

Describe the small and large fragments in the complement system

A

Small - promotes inflammation and chemotaxis

Large - co-locates and binds with antigen to result in membrane attack complex

48
Q

Describe the classic activation pathway of complement cascade to activate antibody

A
  1. Antibody IgM or IgG bind to antigen epitopes causing conformational switch in Fc region
  2. Binding of free Cl proteins to Fc region, Clr activates Cls which is a proteinase allowing subsequent cleavage
  3. Cls cleaves C4
  4. C4b binds to antigen C4a remains in fluid phase - dilation of arterioles and chemotaxis of phagocytes
  5. Cls cleaves C2
  6. C2b binds to antigen C2a remaining in fluid phase
  7. C2b is proteinase which cleaves C3 ** key step **
  8. C3b binds to antigen, C3a remains in the fluid phase and encourages histamine release
  9. C3b cleaves C5 to C5a (fluid phase) and C5b doesn’t spontaneously bind
  10. C5b binds C6, C7 and C8 in fluid phase
  11. C5678 binds to lipid bilayer and rises to membrane attack
  12. C9 (pore forming protein ) inserts hole into membrane
  13. Microorganism is lysed by membrane attack complex
49
Q

Describe opsonisation

A
  • Once phagocytes bind to C3b receptor C21 on phagocyte increases phagocytosis
50
Q

Describe the alternative antibody activation pathway

A

Innate immunity
- Interaction between microbial surface polysaccharide and factors B,D, P interaction activates complement protein c3 activating enzyme cascade therefore opsonisation by C3b

51
Q

What is interstitial fluid?

A

Fluid filling the spaces between cells (interstitial)

52
Q

Describe how interstitial fluid is formed

A
  • Hydrostatic osmotic pressure at arterial ends of capillary beds force fluids with plasma proteins into interstitial space
  • Mostly absorbed at venous ends but more that 3 litres a day remains and needs to be returned to blood
  • lymph capillaries occur alongside blood capillaries and resembles blood capillary but more pores and larger in diameter
53
Q

Describe lymph capillaries

A
  • Endothelial cells and basement membrane have some gaps and some overlapping forming endothelial flaps which act as hinges/ valve with interlinking collagen fibres
  • overlapping cells open when pressure increases allowing fluid into the capillary
  • Anchoring filament allows capillary to not collapse
54
Q

Describe lacteals

A
  • Specialised capillaries in lymph tissue
  • Found in mucosa of intestinal villi
  • Lymph here is milky white due to digestive fast and called chyle
55
Q

Where do larger lymphatic vessels receive blood from?

A

Vasa vasorum

56
Q

Describe the right lymphatic duct

A

Drains at junction of right internal jugular and right subclavian veins

57
Q

Describe the thoracic duct

A

Empties into junction of left internal jugular and left subclavian veins

58
Q

What is the cisternae chyli?

A

Area for lymph collection - lower thoracic duct

59
Q

Describe lymph transport

A
  • Pressure gradient through endothelial flaps
  • Milk action of muscles
  • Breathing induced pressure changes in thorax
  • Rhythmic contraction of smooth muscles
60
Q

Describe lymphoid tissue

A

Loose connective reticular tissue in all lymphatic organs except the thymus, provides attachment points for macrophages and spaces between where lymphocytes can reside

61
Q

Describe diffuse lymphoid tissue

A

Most body organs especially mucous membranes in lymphoid organs

62
Q

Describe follicles/ nodules of lymphatic system

A

Solid tight packed spherical bodes with germinal centres, high proliferative activity lymphocytes undergo clonal expansion and B cell production

63
Q

What is the function of the lymph nodes?

A
  • Filter lymphatic fluid

- Activation of immune system within lymph structure

64
Q

Describe the structure of the lymph nodes

A
  • Fibrous capsules
  • Strands extend into the centre of node and extend into different segments - trabecular with reticular fibres- collagen type 3 with macrophages to filter
  • Framework for macrophages, storm and transient lymphocyte population
  • Cortex is densely packed with follicular structures with germinal centres - delineated by dendritic cells which separate germinal centres from areas in-between where there are transient T cells
65
Q

Describe the afferent and efferent lymph vessels

A

Afferent lymphatic vessels come into lymph node on the convex surface and cavity on the other side forms hills where efferent vessels leave

66
Q

Describe lymph node activation of the immune system

A
  • Outer cortex has lymphatic nodules mainly containing B cells
  • B cells become activated in light zone and produce plasma cells
  • Switching on of Ig class increases affinity for antigen by somatic hypermutation
  • Antigen held by receptor on Fc portion of dendritic cells and B cells undergo clonal expansion in dark zone and compete for binding to antigen
  • Auto reaction from potentially pathogenic autoimmune B cell needs to be helped or it will undergo apoptosis
67
Q

Describe the spleen

A

largest lymphoid organ - secondary organ
Served by splenic artery and saphenous veins that enter hillus on concave side
- Capsule with trabecular, red pulp containing RBC and white pulp containing lymphocytes and macrophages
Splenic cord = site of RBC degradation

68
Q

What is the function of the spleen?

A
  • Lymphocyte generation and immune system surveillance
  • Cleans blood removing old RBC/ platelets
  • Storage of RBC constituents and release of others to liver
  • Storage of platelets
  • Site of RBC production in foetus
69
Q

Describe how RBC’s are filtered through the spleen

A

RBC’s can squeeze through pores in capillary walls and enter Venus sinusoids but fragile RBC’s rupture in this passage and therefore cellular debris which is removed by a macrophage subset found only in the spleen

70
Q

Describe the Thymus

A
Primary lymphoid organ 
- Largest in infants and decreases as age. increases 
- Involved in the endocrine system 
- resembles cauliflower 
- cortex and medullary system - 
Cortex = darker stained packed cells 
Medullary = lighter when stained 
Site of T cell maturation - blood thymus barrier preventing release of immature lymphocytes
71
Q

Describe hassles corpuscle of the thymus

A

Medulla of thymus - contains t lymphocytes, increase of epithelial cells for structural support and negative selection of T cells to generate tolerance against self antigens
- concentric arrangement of flattened epithelial cells, eosinophilic and corratanisation

72
Q

Describe thymus epithelial cells

A

secrete thymus and thymopoeting and thymic factors to stimulate T cell genes Rag 1 /2 Resulting in DNA shuffling to have complete random T cell receptor
- Result in cluster differentiation on precursor cells CD4/CD8

73
Q

Describe positive selection in the thymus

A

Thymic cells recognise precursor cells appropriately, or apoptosis occurs

  • Need presence of MHC-2 to prevent this
  • Apoptosis occurs via secretion of Fas by secretion from lymphocyte of thymic epithelial cells fos binds to immature lymphocyse resulting in specific genes for apoptosis
74
Q

Describe up regulation to increase T helper cells

A

CD4 + MHC down regulation of CD8 and up-regulation of CD4 to produce unique T helper cell

75
Q

Describe up regulation to increase cytotoxic T cells

A

CD8 + MHC down regulation of CD4 and up regulation of CD8 to produce unique T killer cell

76
Q

Describe the tonsils

A

Smallest lymphoid organ

  • 4 sets
  • Palatine - largest tonsils - posterior end of oral cavity
  • Lingual - base of tongue
  • Pharangeal - adenoids in posterior wall of nano pharynx
  • Tubal - surround opening of auditory tubes into pharynx
77
Q

Describe peyers patches

A

Large isolated clusters of nodules similar to tonsil located in walls of ileum

  • Germinal centres
  • Close proximity to lumen
  • Antimicrobial and antibody production
78
Q

What is tolerance?

A

Immune cells non reactivity to antigens

79
Q

What is self tolerance?

A

Tolerance to innate antigens

80
Q

What is neonatal tolerance?

A

Antigens within hours after the birth are tolerated

81
Q

What is acquired tolerance?

A

Development of self tolerance along with self recognition is key in the maturation of both T cells and B cells

82
Q

What are the properties of allergens?

A
  • Small - 15-40000um proteins
  • Soluble
  • Long lasting in environment
  • Low dosage allergen
  • Mucosal exposure
  • Often proteases
83
Q

Describe type 1 hypersensitivity

A

IgE mediated - immediate type hypersensitivity ie allergic asthma, rhinitis
mediated by mast cells

  • Derp 1 cleaves occluding in tight junctions and enters mucosa
  • taken up by dendritic cells for antigen presentation and Th2 priming
  • dendritic cell primes cell in lymph node
  • Th2 cell induces B cell switch to IgE production
  • Plasma cell travels back to mucosa and produces Derp 1 specific antibodies binding to mast cell triggering degranulation - histamine release creating symptoms
84
Q

What are the type 1 mediators of hypersensitivity?

A

Histamine
Lipid mediator - prostaglandins, leukotrienes and platelet activated factor
Chemokine,
Cytokine interleukins

85
Q

Describe type 2 hypersensitivity

A

IgG mediated destruction of blood cells/ platelets autoimmune haemolytic anaemia

  • haemolytic disease in new born thrombocytopenia
  • Antibodies attach to epitopes on self cells inducing compliment cascade
  • Vasodilation and migration of phagocytic cells to the effected area
  • Promotes activation of membrane attack complex
86
Q

Describe type 3 hypersensitivity

A

IgG - immune complex reaction
- Antigen- antibody complex deposits in blood vessel walls causing inflammation and tissue damage
IgG immune complex depositation on vessel walls
Arthus reaction, serum sickness, arthritis, vasculitis, farmers lung

87
Q

Describe type 4 hypersensitivity

A

T cell mediated delayed type sensitivity
Fc triggering of macrophages and neutrophils
- Allergen encounters dendritic cells which bind and activate T cells
- TH effector recognises antigen and releases cytokines acting on vascular endothelium
- Recruitment of phagocytes and plasma to site of antigen injection causing visible legion
Contact hypersensitivity