Lecture 29 - Hypersensitivity

Question 1

Describe the immune response briefly

Answer 1

Antigen invades - recognised by pattern recognition, activation of complement - phagocytosed by dendritic cells - carried to lymph nodes

B cells matured in bone marrow recognise epitope of whole antigen using surface IgD, Endocytose and process antigen

T cells matured and selected in thymus recognise fragment of antigen on classII MHC by dendritic cells - up regulate CD40 costimulatory molecule and cytokine secretion

T and B cells interact in lymph nodes - B cells activated to isotope switch (IgG,A,E) by CD40L on Th2 cells and secrete antibodies

Th1 activate macrophages and tc an migrate into tissues

Question 2

What are the 4 types of hypersensitivity reactions

Answer 2

I - Immediate hypersensitivity (allergy)

AUTOIMMUNITY:

II - autoantibodies

III - deposition of immune complexes

IV - (T) cell mediated tissue injury

Question 3

What is Type I - immediate hypersensitivity

Answer 3

Stimulation of mast cells by cross linking FcR bound IgE

very rapid after exposure to antigen

called allergy or Atopy - strong genetic predisposition - treat with anti-histamines eg. cetirizine

Question 4

What do mast cell mediators cause in Type I hypersensitivity

Answer 4

Increased vascular permeability
Vasodiation
bronchial and sm. muscle con.
local inflammation

Question 5

How do allergens elicit a response

Answer 5

usually require repeated exposure before substance triggers immune response

Many allergens are small, glycosylated molecules with high solubility in body fluids

Dont trigger innate response - no TH1 or macrophage activation

IL-4 promotes TH2 development and antibody class switching to IgE

Question 6

What is Type II -autoantibodies hypersensitivity

Answer 6

3 mechanisms of activation:
Activate complement and stimulate phagocytosis (haemolytic anaemia)

Recuit neutrophils which cause tissue damage (glomerular nephritis)

Can bind to receptor and stimulate or inhibit function (graves disease, MG)

Question 7

How is type II treated

Answer 7

Thionamides (eg. carbimazole)

Anti cholinesterase eg. neostigmine

Question 8

What is type III (immune complexes) hypersensitvity

Answer 8

Systemic disease - Systemic lupus erythematosus (SLE)

Can occur after multiple injections of ag (imuinisation)

Dep. usually occurs in small vas. beds, joints and renal glomeruli

Leads to complement activation and FcR mediated responses

leads to malaria rash and vasculitis

Question 9

How is Type III treated

Answer 9

Steroids

Question 10

What is Type IV (cell mediated tissue injury) hyerpsensitivity

Answer 10

Delayed type hypersensitivity (DTH) and cytotoxicity

Mediated by TH1 and CD8 cells

Release IFN𝛄 to activate macrophages and TNF to induce inflammation

Tissue damage caused by hydrolytic enzymes, ROIs and cytokines

Prototype disease - Type I diabetes

Question 11

How is Type IV treated

Answer 11

Exogeous insulin

Question 12

What is autoimmunity

Answer 12

Results from failure or breakdown in mechanisms normally responsible for maintaining self tolerance

main factors are genetic susceptibility and environmental triggers

Either systemic or organ specific

Various effector mechanisms responsible for tissue injury in autoimmune diseases

Once initiated, can result in epitope spreading in chronic diseases

Question 13

What are some autoimmune diseases

Answer 13

Organ specific - IDDM, MS

Rheumatoid arthritis - inflammation and destruction of joints, abs may also be involved

IBD - mainly mediated by cytokines - can occur following chronic infection - TB

Mainly treated with anti-inflammatory eg. naproxen/steroids and disease modifying agents eg. methotrexate

Question 14

How does genetic susceptibility occur

Answer 14

most diseases polygenic

Inheritance of particular alleles increases risk

Associated with HLA (HLA-DR3 in RA)

HLA-B27 90-100 for increase of Ankylosing spondylitis

most individuals w B27 healthy

Question 15

How is transplantation a form of autoimmune disease

Answer 15

Immune response of recipient to donor tissue

Recognition of donor MHC as foreign

Donor tissue killed by CTL (Tc), T helper cells and abs

Require blood and tissue typing (ABO; HLA systems)

Check for performed antibodies

Graft Versus Host Disease (GVHD)

Question 16

What is blood typing

Answer 16

ABO system - antigens on surface of RBCs

Everyone has basic glycolipid antigen (O), some of attached carbohydrate groups (A/B)

Produce antibodies against antigens we dont have e

Group A has anti B antibodies
Group O has anti A and anti B antibodies

Recipient mustn’t have antibodies against donor antigen

Question 17

How is tumour immunology occuring

Answer 17

Most tumours only weakly immunogenicity - mainly “self”

grow rapidly and overwhelm immune system

Few tumour specific antigens (oncoproteins) or self antigens that are usually hidden

Mainly targeted by CTL and NK cells

Question 18

How are tumours treated

Answer 18

Antibodies, vaccines, costimulatiuon

Question 19

What is tumour immunotherapy

Answer 19

Making tumour more immunogenic

Tagging with antibodies against tumour antigens eg. Herceptin for over expressed HER2

Antbodies against immune regulators eg. ipilimumab to block CTLA-4, nivolumab to block PD-1

Antibody dependent Produg Therapy (ADEPT)

Chimeric antigen Receptor (CAR) - Tc cells

Question 20

What are some forms of immunodeficiency

Answer 20

Congenital
- X-linked agammaglobulinemia
- Severe combined immunodeficiency (SCID)

Acquired
- As a result of infection, cancer or drug treatment (Iatrogenic)
- HIV/AIDS

Question 21

What is HIV

Answer 21

Human Immunodeficiency virus

Infects dendritic cells and carried to lymph nodes

Activation of CTLs and antibody production results in partial control of infection

Infects T cells via CD4 and chemokine receptors

Gradually causes lymphopenia

Patient dies of opportunistic infections