Week 7 - Immunology Flashcards
1
Q
What is haematopoiesis?
A
The process to make cellular elements in the blood
2
Q
What are transferrins?
A
Iron binding proteins that inhibit growth of certain bacteria by reducing available iron therefore reducing bacteria proliferation
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
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
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
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
7
Q
Describe Phagocytes
A
- Recognise pathogens via specific receptors
- Multi-lobular nucleus
- Respond to interleukin
- Differentiate to form macrophages in tissues
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
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
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
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
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
13
Q
Describe kinins
A
- Formed from inactive precursor molecules called kininogens
- Induce vasodilation
- Increase permeability to blood and promotes chemotaxis
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
15
Q
Describe the complement cascade
A
- Associated with release of histamine attraction of neutrophils
- Promotion of phagocytosis and direct bacteria destruction
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
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
18
Q
Describe classically activated monocytes
A
- Defend against bacteria, protozoa and viruses
- Anti-tumour activity
19
Q
Describe alternatively activated monocytes
A
- Anti-inflammatory activity
- Regulate wound healing
20
Q
Describe regulatory macrophages
A
- Secrete large amounts of interleukin-10
21
Q
Describe myeloid derived suppressor cells
A
- Suppress anti tumour immunity
22
Q
Describe Macrophages
A
- upon stimulation they can adopt context dependent phenotypes
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
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
25
Describe T cells
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
26
Describe B cells
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
27
Describe cell mediated immunity
CD8 T cells differentiate into cytotoxic T cells
28
Describe antibody mediated immunity
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
29
Describe antigens
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
30
What are antigens two characteristics?
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
31
Describe MHC Class 1 complex
- Presents self proteins on the surface of the cells
| - MHC1 expressed only on surface of antigen presenting cells
32
Describe MHC class 2 complex
T cells only recognise antigens presented in context on MHC2 achieved through antigen presenting processing
33
describe Exogenous antigen processing
- 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
34
Describe endogenous antigen processing
- 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
35
Describe co stimulation
- 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
Describe binding of MHC 2 with antigen to CD4 T cells
- 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
Describe Cytokines role in the immune system
Small molecules/ growth hormones associated with inflammatory responses and cell replication ie interleukin2/3 and TGF-B transforming growth factor
38
Describe TGF-B
Highly expressed in embryos and neonates, increased concentration decreases scaring so increasing TGF-B induces scarless healing
- Increases survival of damaged cells - BAD
39
Describe interleukin 2 binding
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
describe binging of T cell receptors to MHC2
MHC2 brings cell close and releases perforins and perforates virus infected cell
- gamma inferno activates macrophages and encourages phagocytosis
41
Describe positive selection of T cells
MHC restriction
| - Mediated by thyme epithelial cells in cortex
42
Describe negative selection of T cells
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
Describe the specific antibodies and their function (5)
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
Describe B cell response to antigens
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
What are antibodies function (6)
- 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
What are the two complement activation pathways?
- Lectin pathway
| - Alternative pathway
47
Describe the small and large fragments in the complement system
Small - promotes inflammation and chemotaxis
| Large - co-locates and binds with antigen to result in membrane attack complex
48
Describe the classic activation pathway of complement cascade to activate antibody
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
Describe opsonisation
- Once phagocytes bind to C3b receptor C21 on phagocyte increases phagocytosis
50
Describe the alternative antibody activation pathway
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
What is interstitial fluid?
Fluid filling the spaces between cells (interstitial)
52
Describe how interstitial fluid is formed
- 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
Describe lymph capillaries
- 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
Describe lacteals
- Specialised capillaries in lymph tissue
- Found in mucosa of intestinal villi
- Lymph here is milky white due to digestive fast and called chyle
55
Where do larger lymphatic vessels receive blood from?
Vasa vasorum
56
Describe the right lymphatic duct
Drains at junction of right internal jugular and right subclavian veins
57
Describe the thoracic duct
Empties into junction of left internal jugular and left subclavian veins
58
What is the cisternae chyli?
Area for lymph collection - lower thoracic duct
59
Describe lymph transport
- Pressure gradient through endothelial flaps
- Milk action of muscles
- Breathing induced pressure changes in thorax
- Rhythmic contraction of smooth muscles
60
Describe lymphoid tissue
Loose connective reticular tissue in all lymphatic organs except the thymus, provides attachment points for macrophages and spaces between where lymphocytes can reside
61
Describe diffuse lymphoid tissue
Most body organs especially mucous membranes in lymphoid organs
62
Describe follicles/ nodules of lymphatic system
Solid tight packed spherical bodes with germinal centres, high proliferative activity lymphocytes undergo clonal expansion and B cell production
63
What is the function of the lymph nodes?
- Filter lymphatic fluid
| - Activation of immune system within lymph structure
64
Describe the structure of the lymph nodes
- 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
Describe the afferent and efferent lymph vessels
Afferent lymphatic vessels come into lymph node on the convex surface and cavity on the other side forms hills where efferent vessels leave
66
Describe lymph node activation of the immune system
- 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
Describe the spleen
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
What is the function of the spleen?
- 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
Describe how RBC's are filtered through the spleen
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
Describe the Thymus
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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
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71
Describe hassles corpuscle of the thymus
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
Describe thymus epithelial cells
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
Describe positive selection in the thymus
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
Describe up regulation to increase T helper cells
CD4 + MHC down regulation of CD8 and up-regulation of CD4 to produce unique T helper cell
75
Describe up regulation to increase cytotoxic T cells
CD8 + MHC down regulation of CD4 and up regulation of CD8 to produce unique T killer cell
76
Describe the tonsils
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
Describe peyers patches
Large isolated clusters of nodules similar to tonsil located in walls of ileum
- Germinal centres
- Close proximity to lumen
- Antimicrobial and antibody production
78
What is tolerance?
Immune cells non reactivity to antigens
79
What is self tolerance?
Tolerance to innate antigens
80
What is neonatal tolerance?
Antigens within hours after the birth are tolerated
81
What is acquired tolerance?
Development of self tolerance along with self recognition is key in the maturation of both T cells and B cells
82
What are the properties of allergens?
- Small - 15-40000um proteins
- Soluble
- Long lasting in environment
- Low dosage allergen
- Mucosal exposure
- Often proteases
83
Describe type 1 hypersensitivity
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
What are the type 1 mediators of hypersensitivity?
Histamine
Lipid mediator - prostaglandins, leukotrienes and platelet activated factor
Chemokine,
Cytokine interleukins
85
Describe type 2 hypersensitivity
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
Describe type 3 hypersensitivity
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
Describe type 4 hypersensitivity
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
