Immunology

Question 1

What is hypersensitivity

Answer 1

an exaggerated or inappropriate immune response that causes tissue damage or death of the host.

Question 2

What is a type 1 allergenic reaction
- Response time
- Examples of allergens
- Mediator
- Mechanism
- Diagnostic tese

Answer 2

allergic response within 5-10 minutes of exposure
◦ Origin: —> precipitate B lymphocytes to produce specific IgE with the aid of helper T cells which then bind to and coat mast cell and basophil cells via Fc receptors sensitising them. Later exposure cross links the bound IgE on the surface of the sensitised mast cell triggering degranulation
◦ Allergen/antigen -exogenous substance e.g. pollen, drugs, food
◦ Mediated: IgE —> mast cell degranulation —> histamine, 5 hydroxytryptamine, bradykinin, LK, SRA, PG, platelet activating factor —>oedema and vasodilation, bronchoconstriction —> eosinophils and lymphocytes
◦ E.g. anaphylaxis, asthma (can be local or systemic)
◦ Diagnostic test: skin pric test, IgE serum

Question 3

What is a type 2 allergenic reaction/hypersensitivity reaction
- Response time
- Examples of allergens
- Mediator
- Mechanism
- Diagnostic tese

Answer 3

cytotoxic
◦ Origin
◦ Antigen: cell surface or tissue bound
◦ Mediator: IgG,IgM antibodies binding to cell surface antigen resulting in complement activation through the classical pathways, cell lysis, mast cell activation and neutrophil recruitment. Mobilisation of neutrophils, esoinophils, monocytes and natural killer cells with cell mediated cytotoxicity. Neutrophils recruit and bind IgG and release their granules, and lymphocytes induce apoptosis
◦ Reaction time: 6-36 hours
◦ Mechanism: antibody mediated damage to target cells
◦ Eg. Transfusion reaction, autoimmune haemolysis, myasthenia gravis, glomerulonephritis
◦ Tests: Coomb’s test, ELISA, red cell agglutination,antibody immunofluorescence

Question 4

What is a type 3 allergenic reaction/hypersensitivity reaction
- Response time
- Examples of allergens
- Mediator
- Mechanism
- Diagnostic tese

Answer 4

immune complex
◦ Antigen: exogenous e.g. virus, bacteria, fungi; autoantigens
◦ Mediators: IgG, IgM, IgA, complement
‣ Antigen/antibody complexdeposited in host tissues leading to complement activation —> neutrophil infiltration —> tissue damage. Usually these complexes under normal circumstances are cleared by the reticuloendothelial system however in this circumstance they are too abundant or too small to be cleared effectively
‣ 2 forms
* Complexes formed in circulation then deposited in tissues causing systemic effects e.g. serum sickness
* Complexesformed in tissues causing local effects
◦ Onset: 4-12 hours
◦ Pathology: Vasculitis, neutrophils, acute inflammation
◦ E.g. autoimmune SLE, RA; serum sickness post immunisation
◦ Diagnostic tests: immune complex

Question 5

What is a type 4 allergenic reaction/hypersensitivity reaction
- Response time
- Examples of allergens
- Mediator
- Mechanism
- Diagnostic tese

Answer 5

delayed
◦ Antigen: cell/tissue bound
◦ Mediators: cytotoxic T cells,activated macrophages, lymphokines
‣ Antigen presentation (e.g. langerhans cell) to T lymphocytes (T helper) causing release of cytokines (IL 2, IL 4, IFN alpha) that activate macrophages —> soft tissue injury
◦ Reaction time: 2-3 days
◦ Pathology: perivascular inflammation, mononuclear cells, granulomas, cassation and necrosis in TB
◦ E.g. pulmonary TB, contact dermatitis, graft versus host disease
◦ Diagnostic tests: TB skin test

Question 6

Hypersensitivity reaction times
for each of 1/2/3/4

Answer 6

1 = 5-10 minutes
2 = 6 - 36 hours
3 = 4-12 hours
4 = 2-3 days

Question 7

What is an example of a type 2 or cytotoxic hypersensitivty reaction? How would you test for it?

Answer 7

Transfusion reaction, autoimmune haemolysis, myasthenia gravis, glomerulonephritis

Test: Coomb’s test, ELISA, red cell agglutination,antibody immunofluorescence

Question 8

How does a cytotoxic hypersensitivyt reaction occur?

Answer 8

◦ Antigen: cell surface or tissue bound
◦ Mediator: IgG,IgM antibodies binding to cell surface antigen resulting in complement activation through the classical pathways, cell lysis, mast cell activation and neutrophil recruitment. Mobilisation of neutrophils, esoinophils, monocytes and natural killer cells with cell mediated cytotoxicity. Neutrophils recruit and bind IgG and release their granules, and lymphocytes induce apoptosis

Question 9

Immune complex or type 3 hypersensitivty reactions are caused by?

Answer 9

exogenous e.g. virus, bacteria, fungi; autoantigens

Question 10

Immune complex or type 3 hypersensitivty reactions mechanism

Answer 10

IgG, IgM, IgA, complement
‣ Antigen/antibody complexdeposited in host tissues leading to complement activation —> neutrophil infiltration —> tissue damage. Usually these complexes under normal circumstances are cleared by the reticuloendothelial system however in this circumstance they are too abundant or too small to be cleared effectively
‣ 2 forms
* Complexes formed in circulation then deposited in tissues causing systemic effects e.g. serum sickness
* Complexesformed in tissues causing local effects

Question 11

Types of type 3 hypersensitivity reactions?

Answer 11

Vasculitis, SLE< RA, serum sickness post imunisation

Question 12

Delayed type 4 hypersensistiivty reactions mechanism

Answer 12

cytotoxic T cells,activated macrophages, lymphokines
‣ Antigen presentation (e.g. langerhans cell) to T lymphocytes (T helper) causing release of cytokines (IL 2, IL 4, IFN alpha) that activate macrophages —> soft tissue injury

Question 13

How long does antigen exposure to targeted immune response take?

Answer 13

5 days

Question 14

Immunisation is

Answer 14

• Immunization: A process by which a person becomes protected against a disease through vaccination. This term is often used interchangeably with vaccination or inoculation.

Question 15

What is a vaccine

Answer 15

• Vaccine: A product that stimulates a person’s immune system to produce immunity to a specific disease, protecting the person from that disease.

Question 16

Why is immunisation valuable?

Answer 16

◦ by utilising antigen presentation allowing primary immune response to occur in the absence of clinical infection
◦ allowing maturation of the targeted immune response improving the speed, size and specificity of future responses to the matching epitope in the case of clinical infection.

Question 17

What are the two methods of immunisation? Explain what is required for each to work? Examples of each vaccine? Permanency of immunity from each method

Answer 17

Immunisation can be performed through active or passive approaches
* Active - inactive portion of virus or bacterium given to the patient, usually through injection. Requires immunocompetent response to exposure to work. Produces long term immunity
* Passive - preformed antibodies given to the patient who is unimmunised
◦ Physiological - antibodies from mother across placenta to foetus , and through breast milk
◦ Clinical - recombinant antibodies e.g. varicella zoster immunoglobulin; pooled IVIG and antivenom
◦ Effect - develop temporary immunity to the particular organism or toxin, once these preformed antibodies are destroyed you will not longer have immunity

Question 18

Describe the process of antigen –> adaptive immunity

Answer 18

• Antigen identified by antigen presenting cell (dendritic cell, macrophage) which phagocytise the antigen which is then incorporated into MHC class 2 on the surface of the cell as it transits to nearby lymphoid tissue e.g. lymph node
• APC presents the antigen complex on the surface fo the cell to multiple B cells and T helper cells —> when there is a receptor match antibodies are produced
  ◦ Viral: Antigen + MHC I complex → presented to CD8 cell → trigger cell mediated immunity
  ◦ Bacterial or parasitic: Antigen + MHC II protein → presented to CD4 cell → trigger antibody- mediated immunity
• T helper cells become activated when the T cell receptors (CD4) matches the APC antigen
  ◦ Become blast cells cells —> rapid proliferation (cloning self) —> small proportion become memory T helper cells that assist in later activation
  ◦ Cell mediated response where cytotoxic T cells are activated binding to MHC 1 on antigen cells
• B cells - usually requires T helper cell coactviation (safety system) —> rapidly divide —> plasma cells and memory cells
  ◦ Plasma cells produce antibodies which then
  ‣ Opsonise the pathogen - identify it for leukocytes facilitating phagocytosis
  ‣ Agglutination - cause pathogens to clump
  ‣ Inactivate - if the binding site has important functions, or inactivate a toxin
  ‣ Activate complement - classical pathway aids phagocytosis through chemotaxis and opsonisation,mast cell degranulation
  ◦ The initial response of B cells to primary infection is to produce IgM antibodies, however with secondary infection IgG response is also involved

Question 19

What are antigen presenting cells

Answer 19

Dendritic cells, macrophages, B cells in certain circumstance

Question 20

What cell membrane protein does an antigen presenting cell have that is significant

Answer 20

MHC 2

Question 21

What does a CD8 cell require to be activated

Answer 21

MHC1 with a recognised antigen

Question 22

What cell does an antigen presenting cell go to?

Answer 22

T helper cell

Question 23

B cells require what to activate

Answer 23

T helper cells for coactivation to division into plasma cell and memory cells

Question 24

What is the function of plasma cells

Answer 24

‣ Opsonise the pathogen - identify it for leukocytes facilitating phagocytosis
‣ Agglutination - cause pathogens to clump
‣ Inactivate - if the binding site has important functions, or inactivate a toxin
‣ Activate complement - classical pathway aids phagocytosis through chemotaxis and opsonisation,mast cell degranulation

Question 25

Triggers for anaphylaxis

Answer 25

‣ food, environmental ‣ Drugs - Abx, muscle relaxants ‣ Iodine contrast ‣ Chlorhexidine ‣ Latex

Question 26

Describe how allergy develops

Answer 26

‣ First exposure - allergen presented to T helper cells --> presents to B cells ‣ Precipitate B lymphocytes to produce specific IgE to allergen which circulate ‣ IgE then bind to and coat mast cell and basophil cells via Fc receptors sensitising them.

Question 27

Describe how exposure progresses to anaphylaxis

Answer 27

‣ Later exposure cross links the bound IgE on the surface of the sensitised mast cell triggering degranulation ‣ Degranulation releases * histamine - local release --> urticaria, systemic leads to vasodilation and increased vascular permeability * 5 hydroxytryptamine - vasodilates, bronchoconstriction, platelet activation * bradykinin - increased production of PGI2 and NO leading to increased vascular permability and reduced MAP * LK - LTE B4 chemotactic agent, D4 and E4 cause angiooedema, clotting, thrombolysis * TNF alpha - propogates action * PG - PGI2 vasodilation, increased permeability and bronchoconstriction. Activates eosinophils * Platelet activating factor ◦ Combined effect —>oedema and vasodilation, bronchoconstriction —> eosinophils and lymphocytes ‣ Severe circulatory collapse, distributive shock with profound vasoplegia ‣ Airway obstruction, angiooedema and bronchospasm ‣ Urticaria ‣ Abdominal pain, vomiting

Question 28

What are the mediators of anaphylaxis? Describe each's action

Answer 28

‣ Degranulation releases * histamine - local release --> urticaria, systemic leads to vasodilation and increased vascular permeability * 5 hydroxytryptamine - vasodilates, bronchoconstriction, platelet activation * bradykinin - increased production of PGI2 and NO leading to increased vascular permability and reduced MAP * LK - LTE B4 chemotactic agent, D4 and E4 cause angiooedema, clotting, thrombolysis * TNF alpha - propogates action * PG - PGI2 vasodilation, increased permeability and bronchoconstriction. Activates eosinophils * Platelet activating factor Combined effect —>oedema and vasodilation, bronchoconstriction —> eosinophils and lymphocytes ‣ Severe circulatory collapse, distributive shock with profound vasoplegia ‣ Airway obstruction, angiooedema and bronchospasm ‣ Urticaria ‣ Abdominal pain, vomiting

Question 29

Management of anaphylaxis

Answer 29

Oxygen IV fluids Lie them down - no standing Adrenaline

Question 30

Describe the pharmacology of adrenaline in anaphylaxis

Answer 30

◦ Stabilises mast cells to prevent degranulation ◦ Low doses: Beta agonism at (inotropy and chronotropy) and causing smooth muscle relaxation (including bronchorelaxation). ◦ Higher doses: alpha effects and causes vasoconstriction. ◦ In adults, 0.3-0.5mg IM Q5-15min ◦ In children, 0.01mg/kg IM Q5-15min

Question 31

What use does glucagon have in anaphylaxis? How would you use it?

Answer 31

* Glucagon may be used in β-blocked patients resistant to adrenaline. ◦ In adults, 1-5mg IV over 5 minutes, followed by infusion at 5-15microg/min ◦ In children, 20-30mcg/kg up to 1mg over 5 minutes

Question 32

Adjunctive agents in anaphylaxis may be

Answer 32

Steriod Antihistamine Salbutamol

Question 33

Action of steriod in anaphylaxis?

Answer 33

‣ Work by binding to the cell nucleus and switching off the transcription of various genes which encode for inflammatory mediators such as cytokines, chemokines, adhesion molecules and arachidonic acid. ‣ They also activate anti-inflammatory genes such as MAP (mitogen activated protein) and increase the expression of beta2 receptors. ‣ Methylprednisolone, Hydrocortisone or Prednisolone

Question 34

Action of antihistamine in anaphylaxis

Answer 34

‣ Binds to H1 receptors to block the effects of the histamine released from mast cells- ‣ inhibition of vasodilatation ‣ increased vascular permeability ‣ contraction of non-vascular smooth muscle ‣ Diphenhydramine 25-50mg IV (Children: 1mg/kg up to 40mg) up to 200mg in 24/24

Question 35

What is a lymphocyte

Answer 35

immunologically competent cells that assist and add specificity to the defence of the body making up 20-40% of the white cells in the body

Question 36

Describe the origin of T and B lymphocytes

Answer 36

* Origin ◦ Bone marrow is the primary lymphopoetic organ where lymphocytic cells are produced in post natal life ‣ In the foetus the yolk sac, liver and spleen are the primary sites ‣ Secondary sites: lymphoid tissue in lymph nodes, spleen adn respiratory tract ◦ Derived from the same common Lymphoid progenitor stem cell in foetal bone and complete their development either ‣ In the bone itself --> B lymphocytes --> migrate to lymphoid tissue and are called plasma cells to produce antibodies ‣ In the thymus where only 2% of immature T cells survive --> T lymphocytes - after migrating there they mature and leave to peripheral lymphoid tissue

Question 37

Relative distribution of circulating lymphocytes

Answer 37

◦ T - 60-80% of circualting lymphocytes, 90% of thoracic duct lymphocytes ◦ B - predminant lymphocytes in bone marrow nad germinal centres of lymph node follicles, 5-15% of circulating lymphocytes ◦ Both are primarily stored in thymys, spleen, submucosa of GIT, bone marrow and lymph glands

Question 38

Describe the secondary specialisation of T lymphocytes

Answer 38

◦ T lymphocytes - helper and suppresor cells ‣ As they migrate from the thymic cortex to the medulla they lose and gain antigens ‣ Helper cells - CD4 membrane protein antigens - 2/3 of T cells. * Functions ◦ Cytokine production ◦ B lymphocyte stimulation ◦ Macrophage activation ‣ Suppressor cells - CD8, CD2, CD3, others ‣ Cytotoxic T cells - CD8 membrane protein * Destroy virally infected and tumour cells - all express proteins that they are producing on membrane MHC 1 molecules for immune cell inspection. Foreign proteins are recognised causing activation inducing apoptosis of the target cells and rapid division of cytotoxic T cell which then inspects other cells and forms memory cells

Question 39

Describe the function of a T helper lymphocyte

Answer 39

◦ Produce a wide range of lymphokines - IL2, IL3, IL6, alpha and gamma interferon, lymphotoxins, TNF and beta cell growth factor which ‣ attract and activate macrophages ‣ encourage proliferation of cytotoxic and suppressor T cells ‣ stimulate B cell proliferation and differentiation

Question 40

How do you active a T helper cell?

Answer 40

activated by MHC class 2 bound antigens (macrophages or dendritic cells)

Question 41

What are lymphokines?

Answer 41

Chemokines causing WCC chemotaxis derived from lymphocytes IL2, IL3, IL6, alpha and gamma interferon, lymphotoxins, TNF and beta cell growth factor

Question 42

What proportion of T cells are T helper cells

Answer 42

2/3

Question 43

What maturation process occurs in the thymus for T cells

Answer 43

‣ As they migrate from the thymic cortex to the medulla they lose and gain antigens

Question 44

Cytotoxic T cells perform what function? What activates them? How do they then act

Answer 44

CD8 membrane protein * Destroy virally infected and tumour cells - all express proteins that they are producing on membrane MHC 1 molecules for immune cell inspection. Foreign proteins are recognised causing activation inducing apoptosis of the target cells (via release of perforins and released cytotoxins) and rapid division of cytotoxic T cell which then inspects other cells and forms memory cells

Question 45

Actions of immunoglobulins

Answer 45

‣ Antibody production which act against non self antigens --> attacking non self antigens by agglutination, opsonisation or complement activation. Actions described by PLAN * Opsonisation and precipitation * Lysis - antibody/antigen complex activates complement cascade causing pathogen damage and recruiting phagocytes and local elimination * Agglutination - each antibody can bind multiple pathogens increasing target size for leucocytes * Neutralisation

Question 46

What is the lifespan of T and B lymphocytes

Answer 46

* Lifespan and degredation ◦ T lymphocytes - long lived - 6-12 months, as memory B cells can reactive ◦ B lymphocytes - short lived plasma cells, memory B cells last years

Question 47

Describe in brief the activation of the adaptive immune response

Answer 47

* Process of invasion of a new pathogen takes 5 days * Antigen presenting cell phagocytose a pathogen e.g. macrophages and dendritic cells ◦ They then prresent antigens (bits of pathogen) on cell surface ◦ Travel to lymphoid tissue and present to B and T cells * When APC binds to a B or T cell with reciprocal antibody ◦ T helper cell activated by APC ‣ Rapidly proliferates with clonal expansion and proportion become memory cells ◦ B cells then activated by both APC AND T helper cell (requires both) ‣ Rapidly proliferate as memory and plasma cells ‣ Plasm a cells produce antibody at a rate of 2000 molecules per second overriding cellular homeostasis and causing death within a week (primary immune response = IgM

Question 48

Describe 5 non immune host defenses

Answer 48

* Skin ◦ Physical barrier to tissue access - 3 layers of closely packed cells (epidermis, dermis, hypodermis) ‣ Continual shedding in addition tot he thick barrier removes agents from the skin surface ‣ Tightly connected dense cell husks in the epidermis resistant to degredation ◦ produces lactic and fatty acids which prevent bacterial growth - inhibit growth and are resistant to breakdown by bacterial enzymes * Mucous membranes ◦ Layer of epithelial cells bound by tight junctions foudn in nose, mouth, lungs, urinary and digestive tracts ◦ Mucous traps bacterial particles then removed by ciliary motion ◦ Antimicrobial secretions - lysosymes in tears, prostatic fluid, cervical mucous ◦ Immunoglobulins IfA and IgG preventing attachementto host cells * Airway ◦ Coughing, sneezing expels organissm ◦ Mucociliary elevator ‣ Respiratory tract * Gut ◦ Acidic environment of the stomach is bacteriocidal ◦ Microbiome - natural gut flora compete against disease for nutrition; similar mechanisms also important in the upper respiratory tract, genitourinary tract ◦ Gut transit preventing prolonged bacterial dwell times for expansion * Urination - ◦ high flow rates ◦ Long ureteral length ◦ low residual bladder volumes ◦ tight junctions preventing migration between cells ◦ Acidic pH and hypertonic ◦ Tamm Horsfall mucoprotein binding bacteria * Eye mechanisms ◦ Physical barriers - eyelashes and eyelids ◦ Flushing mechanism of tears

Question 49

Describe mechanisms of the skin as non immune host defense 3

Answer 49

◦ Physical barrier to tissue access - 3 layers of closely packed cells (epidermis, dermis, hypodermis) ‣ Continual shedding in addition tot he thick barrier removes agents from the skin surface ‣ Tightly connected dense cell husks in the epidermis resistant to degredation ◦ produces lactic and fatty acids which prevent bacterial growth - inhibit growth and are resistant to breakdown by bacterial enzymes

Question 50

Describe non immune host defences of mucous membranes 4

Answer 50

◦ Layer of epithelial cells bound by tight junctions foudn in nose, mouth, lungs, urinary and digestive tracts ◦ Mucous traps bacterial particles then removed by ciliary motion ◦ Antimicrobial secretions - lysosymes in tears, prostatic fluid, cervical mucous ◦ Immunoglobulins IfA and IgG preventing attachementto host cells

Question 51

Describe airway non immune host defenses 2

Answer 51

◦ Coughing, sneezing expels organissm ◦ Mucociliary elevator ‣ Respiratory tract

Question 52

Describe gut non immune host defenses (3)

Answer 52

◦ Acidic environment of the stomach is bacteriocidal ◦ Microbiome - natural gut flora compete against disease for nutrition; similar mechanisms also important in the upper respiratory tract, genitourinary tract ◦ Gut transit preventing prolonged bacterial dwell times for expansion

Question 53

Describe urinary non immune host defenses (5)

Answer 53

◦ high flow rates ◦ Long ureteral length ◦ low residual bladder volumes ◦ tight junctions preventing migration between cells ◦ Acidic pH and hypertonic ◦ Tamm Horsfall mucoprotein binding bacteria

Question 54

What are key features and elements of the innate immune system? If you had to define it how would you do it?

Answer 54

* Lifelong protective mechanisms with action independent of previous exposure forming the first line of defence by recognising generic pathogenic motifs and directly attack or opsonize and phagocytose ◦ Key features ‣ Immediate action ‣ Non specific ‣ Not modified by previous exposures ◦ Elements ‣ Physicochemical barriers ‣ Humeral mechanisms ‣ Cellular mechanisms

Question 55

What is a cytokine

Answer 55

◦ Cytokines - produced primarily by macrophages and lymphocytes and are potent polypeptides acting on toher cells via cell membrane receptors. (lymphokines are cytokines from lymphocytes; monocytes produce monokines). The difference to hormones is that hormones are chemical messengers from ductluss glands secreted into the blood stream to affect target cells distantly via specific receptors - cytokines are not produced by special glands, and most have paracrine or autocrine action. ‣ IL 1 and 6 ‣ TNF alpha ‣ interferon ‣ Chemokines - chemotactic cytokines attract immunological cells

Question 56

If you were to separate the innate immune system into 3 categories what would they be

Answer 56

Non immune host defenses Humoral innate mediators - complement, cytokines, lysosomes Innate immune cells

Question 57

List 4 cytokines

Answer 57

‣ IL 1 and 6 ‣ TNF alpha ‣ interferon ‣ Chemokines - chemotactic cytokines attract immunological cells

Question 58

What are 5 non cytokines humoral innate agents?

Answer 58

◦ Defensins – perforate pathogenic membranes ◦ Complement ◦ Lysosomes ◦ CRP ◦ Fibronectin ◦ Alpha 1 antitrypsin

Question 59

Complement - the role is to? How many proteins? What pathways are there? Functions 3

Answer 59

◦ opsonize and signal for phagocytosis and directly lyse via membrane attack complex ◦ 25 heat labile plasma proteins important in innate and adaptive immunity ◦ Activated by ‣ Antigen/antibody complex - classical pathway ‣ Substances in the bacterial cell wall - alternative pathway ◦ Functions ‣ Destructrion of bacteria - membrane attack complex ‣ Identify and mobilise immune cells * Opsonisation of bacteria - binding sites for phagocytes * Chemotaxis - attracting leucocytes * Activation of monocytes and phagocytes ‣ Mast cell degranulation augmenting inflammation

Question 60

Name 4 innate immune cells

Answer 60

Neutrophil Basophil Eosinophil Dendritic cell NK cell Macrophages Mast cell

Question 61

Neutrophils make up what % of leucocytes?

Answer 61

60%

Question 62

How many bacteria can a neutrophil phagocytose

Answer 62

15-20

Question 63

How does a neutrpohil enter inflamed tissue and kill bacteria

Answer 63

* Marginate along capillary border when activated by inflammatory mediators * Migrate via chemotaxis towards tissue insult - capillary permeability is increased by histmaine, kinins, bacterial products including endotoxin and exotoxin * Phagocytose opsonised bacteria and fungi * Kill organisms via degranulate cytotoxic contents and cause oxidative damage to pathogens (hydrogen peroxide, hydroxyl, oxygen free radicals)

Question 64

What is the difference between a a macrophage and a monocyte?

Answer 64

monocytes become macrophages when they leave circulation and enter tissue

Question 65

How long does a macrophage live

Answer 65

2-4 months

Question 66

Functions of macrophages

Answer 66

* Phagocytose and kill opsonized pathogens esp intracellular pathogens e.g. listeria, mycobacteria; parasites, fungi * Breakdown damaged body cells * Antigen presenting cell to T helper cells * Secreting inflammatory mediators

Question 67

What is a natural killer cell? What is its function?

Answer 67

‣ Recognize abnormal cell surface expression (e.g. lack of MHC, abnormal MHC proteins) due to intracellular pathogens (e.g. virus) and directly kill infected cells, but also malginant body cells and invading organisms ‣ Lymphocytic derived however lack antigen recognition molecules for antibodies or T cell receptors ‣ No memory, no prior sensitisation necessary

Question 68

Where do mast cells reside

Answer 68

loose connective tissue and mcuosa

Question 69

What is in a mast cells granules

Answer 69

histamine, heparin

Question 70

What is the MHC system? What idd it used to be known as? What is the difference between class 1 and 2? Why cannot all CD8 cells recognise MHC1 antigens?

Answer 70

* Cell membrane proteins which bidn short peptide antigens and present them to cells of immune system * Class 1 - two proteins, membrane spanning MHC protein bound to beta 2 microglobulin ◦ All cells in the body have MHC class 1 proteins on thier surface ‣ 3 class 1 genes - and each class 1 membrane spanning protein has 2 of these i.e. 6 combinations ◦ When cells are invaded foreign antigens are degraded within the cells to produce peptides which become bound to MHC class 1 proteins and expressed on external membrane which are recognised by B or specific cytotoxic T lymphocytes * Class 2 ◦ two membrane spanning proteins produced only in macorphages, dendritic cells and some B cells (APC) ◦ Proteins degraded within these cells from external sources ◦ Activate T helper cells * MHC restriction - T cells recognise the combination of the peptide and antigen as cytotoxic T cells are restricted to the exam antigenic peptide and MHC combination (same peptide on another MHC molecule doesnt work)

Question 71

What is MHC restriction?

Answer 71

T cells recognise the combination of the peptide and antigen as cytotoxic T cells are restricted to the exam antigenic peptide and MHC combination (same peptide on another MHC molecule doesnt work)

Question 72

What is complement?

Answer 72

* Proteolytic system of the plasma with 25 plasma proteins * Two potential reeaction pathways linked by a final common pathway

Question 73

Describe the classical complement pathway?

Answer 73

* Activated by antigen-antibody complex - IgM or certain IgG * 11 enzymes circulating as inactive precursers - C1 (3 subtypes), C2, C3, C4 - C9 * C1q binds to complex --> activates C1r --> activates C1s * C4 and C2 then react to form an enzymatic complex known as C3 convertase forming C3b and C3a

Question 74

Describe the alternative complement pathway

Answer 74

* Activated in absence of antibodies - C3 undergoes slow spontaneous conversion to hydrolysed C3 * Interacts with factors B and D tof orm complex splitting small amounts of C3 --> C3a and C3b * C3b interacts with certain bacteria cells and B and D to form a more potent C3 convertase resulting in a similar progression of activation * C3b combines with C3 convertase of the alternative pathway to progress the steps

Question 75

Common complement pathway

Answer 75

* Commences at the breakdown of C3 ◦ C3b and C3 convertase combine to form C5 convertase splitting it into a and b components ‣ C3b also acts as an opsonin coating target cells providing site for phagotcytesto bind ◦ C5b now reacts with terminal complement components C 6 - 9 to form membrane attack complex inserting itself into cel membranes forming pores or channels leading to cell lysis (cellular swelling)

Question 76

What are anaphylactotoxins?

Answer 76

* C3a and C5a are anaphylactotoxins ◦ C3a degranulates mast cells releasing histamine ◦ C5a degranulates mast cells, neutrophils and basophils --> degranulation, neutrophil aggregation, local vasodilation and chemotaxis

Question 77

What regulates complemetn

Answer 77

C1 esterase inhibitor

Question 78

Overall complement effects 4

Answer 78

* Cell lysis of bacteria * Opsonisation and optimisation of phagocytosis * Inflammation - mediators such as histamine release * Chemotaxis and neutrophil aggregation - C5a