I&I ESA Stem

Immunology only

• What is innate immunity– Non-specific immediate immune response to antigens

• What are the components of innate immunity– Physical

• Skin• Secretions• Mucus• Normal bacterial flora

– Cellular• Macrophages• Neutrophils• Eosinophils• Basophils and mast cells• Natural killer cells

– Humoral• Complement• cytokines

• What is adaptive immunity– Specific response to presented antigen that is more delayed than

innate• What are the components of adaptive immunity

– Cellular• T-lymphocytes

– Helper (CD4)» T1 = help macrophages» T2 = help B-cells

– Cytotoxic (CD8) /killer

– Humoral• B-lymphocytes/plasma cells/memory B-cells• Antibodies

– IgG, IgA, IgM, IgE, IgD

• Explain the role of MHC/HLA in antigen presentation– Class I• Presented on all nucleated cells• Present host, viral or neoplastic antigens to Tc-cells

– Class II• Presented on antigen-presenting cells only• Presents engulfed microbe antigens to Th-cells

– Th-cells stimulate B-cells to produce antibodies

• Why is the process of tolerance important and when does it develop– Tolerance of self antigens is essential to prevent

autoimmunity– In the neonatal period

• Foetus’s and neonates treat everything as “self”

• Explain how tolerance develops– During lymphocyte development B and T cell receptor are

formed by random gene recombination (against both foreign and self)

– The “self” receptors are eliminated leading to self tolerance

• Definition of allergy– Hypersensitivity to a substance considered

harmless to most people• What is atopy– Genetic tendency to develop classic allergic

disease

• What are the main mediators of the 4 types of hypersensitivity– Type 1

• IgE

– Type 2• IgM

– Type 3• IgG

– Type 4• T-cell

• Describe the stages of allergy– Allergen exposure– Sensitization– Specific IgE production– Re-exposure to allergen– Acute allergic response -anaphylaxis• Via Th2-cells

• What is the triad of atopy– Rhinoconjunctivitis (hayfever)– Allergic asthma– Atopic dermatitis (eczema)

20yr old Nikseh Marchal is rushed to A&E after accidentally ingesting peanuts. He is tachycardic and tachypnoeic with laryngeal oedema and a generalised rash and is drifting in and out of consciousness

• What is his diagnosis– Anaphylaxis

• What is the pathophysiology of his symptoms– Release of inflammatory mediators– Increased vascular permeability and vasodilation

• What is you immediate course of action– Standard ABC approach– Inject adrenaline (epi pen)– Give paraenteral antihistamine– corticosteroids

• How would you investigate a patient with suspected allergy– Skin prick test– Patch testing– Intradermal testing– Radioallergosorbent test

• How do you manage a patient with an allergic disease– Allergen avoidance– Patient education– Symptomatic relief (anti-histamines)– Immunomodulatory therapy

• Specific allergen immunotherapy (desensitization)• Anti-IgE monocloanal Ab

• What is autoimmunity– Immune reaction against self

• What parts of the immune system are involved– B-cells and autoantibodies– Autoreactive T-cells– Cytokines – complement

• What are the mechanisms of autoimmunity– Inappropriate triggering of immune response– Molecular mimicry (own cells resemble foreign antigen)– Failure to suppress auto-reactive cells– Exposure of immune privileged cells to immune system

27yr old Marsha Walsh attends clinic complaining of fatigue and joint pain. you also notice that she is uncomfortable when you turn on a bright light and she has a butterfly rash across her cheeks

• What is your suspected diagnosis and the underlying pathology– Systemic lupus erythematosis– Deposition of immune complexes

• How will you treat Marsha– Symptomatic treatment with NSAIDs– Immunosuppressants

• Corticosteroids for flare ups• Cyclophosphamide to achieve remission• Azathioprine to maintain remission

40yr old Mada Heskin is on the waiting list for a kidney transplant

• How is a good donor match for transplantation determined– HLA matching• 3 loci in humans A, B and Dr each with 2 copies• 6 alleles

Mada goes on to receive his transplantation. You are now concerned with rejection

• Describe the 3 types of rejection– Hyperacute

• Graft goes black on the table• Vascular rejection• Due to complement and preformed antibodies

– Acute• Abrupt onset with rapid decline in function• Abs and T-cell mediated but not preformed• Usually reversible by immunosuppressants

– Chronic• Irreversible slow/longterm decline in function• Initiated by chronic immune damage leading to fibrotic repair

– Subsequent vascular damage

In order to prevent rejection, Mada is put on immunosuppressants

• What are the main targets of immunosuppression– IL-2 production– T-cell response– Proliferating lymphocytes– Inflammation– Activated lymphocytes

• What are some complications of immunosuppression– Infections– Cardiovascular disease– Diabetes– nephrotoxicity

Mada ended up having to have a bone marrow transplant (bad new bears!) and goes on to develop a rash on his hands and feet that then spreads over his body.

• What is your suspected diagnosis– Graft vs host disease

• What is the pathophysiology of this disease– Host is unable to reject graft– Graft lymphocytes are activated by host antigens

and damage host tissues• How will you treat Mada– Early treatment with corticosteroids

• What are primary and secondary immunodeficiencys– Primary – intrinsic defects of haematological

system usually genetic defects– Secondary –defects of haematological system

acquired due to external factor

• What are the different types of immunodeficiencies and give an example of each– Immunoglobulin deficiency

• Primary – Brutons X-linked agammaglobin– CVID

• Secondary– Nephrotic syndrome– Chronic B lymphocytic leukaemia

– T-cell deficiencies• Primary

– SCID– DiGeorge syndrome

• Secondary– HIV

– Complement deficiencies– Neutrophil deficiencies

• Primary– Chronic granulomatous disease

• Secondary– Neutropenia

• What is the typical presentation of immunodeficiency– Failure to thrive– Enhanced susceptibility to infection (SPUR)• S - serious• P – persistent• U - unusual• R – recurrent

– Jaundice, diarrhoea, rashes

• what is the pathology and treatment of bruton’s X-linked agammaglobulinaemia– Boys without B-cells – no b-cells = no Ig– IV Ig treatment

• what is the pathology and treatment of common variable immunodeficiency– B-cells normal but plasma cell differentiation

defective = no/impaired Ig production– IV Ig treatment

• what is the pathology and treatment of severe combined immunodeficiency– Defect in lymphocyte development

• Always T-cells, sometimes B-cells/NK cells

– Treatment• Maintenance

– Barrier nursing (bubble kids)– Prophylactic antibiotics– IV Ig

• Curative– Stem cell CD34 cell transplant– Gene therapy

• what is the pathology and treatment of DiGeorge syndrome– Thymic hypoplasia = few t-cells– Treatment

• Maintenance – prophylactic antibiotics• Curative – thymic transplantation using foetal tissue or stem cells from HLA

identical siblings

• With reference to DiGeorge syndrome, what is catch 22– Cardiac defects– Abnormal facies– Thymus hypoplasia– Cleft palate– Hypoparathyroidism– Chromosome 22

• what is the pathology and treatment of chronic granulomatous disease– X-linked deficiency in NADPH oxidase enzyme

leads to inability to destroy phagocytised material– treatment• Prophylactic antibiotics• Bone marrow transplant

• Briefly describe the 3 main types of haemopoietic malignancies– Leukaemia

• Cells proliferate in bone marrow resulting in overspill of immature cells into blood

– Lymphoma• Mature lymphocytes proliferate in nodes and cause swelling

– Not present in circulation

– Myeloma• Plasma cells proliferate in bone marrow

– Not present in circulation