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Immunology for NL

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Immunology for NL 2009



Surasak Wongratanacheewin,

sura_wng@kku.ac.th

You must know (at least)

• Hypersensitivity

• Ab- IgG, IgM (Immunization and vaccines)

• Primary and secondary immune response

• T cell recognition to MHC I, II

• Immunity to infections

• Serological methods

• Transplantation

• Autoimmunity

Hypersensitivity

• Immediate Hypersensitivity • Delayed-Type Hypersensitivity

Reactions Reactions



• Anaphylactic reactions of • Inappropriate reactions of the

humoral immune response cell-mediated immune response



• Symptoms manifested within • Symptoms manifested sometime

minutes to hours of antigen after 24 hours of antigen

recognition recognition



• Different antibody isotypes • Effector molecules are the

induce different immune effector cytokines secreted by activated

molecules TH or TC cells



• Type I (IgE mediated), Type II • Type IV (cell mediated

(antibody-mediated) and Type III hypersensitivity)

(immune complex-mediated)

Hypersen I

• Type I, IgE-Mediated Hypersensitivity



• Abnormal humoral response induced by allergens



• Allergens: non-parasitic antigen capable of stimulating

type I hypersensitivity in allergic people



• Atopy: hereditary predisposition to develop immediate

hypersensitivity reactions to common environmental

antigens

Hypersen I

• Mechanisms triggering

degranulation of mast cells



• Generally initiated by

allergen cross linking bound

IgE



• Other initiators:



• Anaphylatoxins (C3a, C4a,

C5a)



• Drugs

• What are the mediators released by mast cells and basophils?



• Ex. Histamine binding to H1, H2, H3 receptors, Leukotrienes and

prostaglandins (degranulation leads to synthesis), cytokines (alter local

inflammation and recruit neutrophils and eosinophils)

Hypersen I

• Location of allergic

responses



• On mucous membranes in

response to inhaled or

ingested antigens



• Allergen are diverse in

structure



• Complex interactions

results in allergic

response;

Hypersen I

• Type I Reactions are systemic or • Localized Anaphylaxis (Atopy)

localized

• Reaction is limited to specific

• Systemic Anaphylaxis

tissue or organ

• Shock-like and often fatal

• Tendency for localized response is

• Rapid onset inherites (atopy)

• Contraction of smooth muscle (GI

and bladder), vasodilation (drop • Types: allergic rhinitis (hay fever),

in blood pressure), bronchiole asthma, eczema (atopic

constriction (asphyxiation) dermatitis), and food alergies

• Edema, shock and bronchiole

constriction lead to death • Late phase reactions induce

localized responses

• Treatment: epinephrine

• Localized inflammation following

granulation

• Controlling type I reactions



• Avoidance of allergens



• Immunotherapy with repeated subcutaneous injections doses of allergens

(generation of an IgG blocking Ab)



• Use of drugs to inhibit biochemical steps leading to degranulation

Hypersen II

• Type II Hypersensitivity • Three types

• IgG-Mediated Cytotoxic

Hypersensitivity • Transfusion reactions

• Antibody-mediated destruction of

cells • Hemolytic disease of

newborns

• Can activate complement



• Can mediate cell destruction by • Drug-induced hemolytic

antibody dependent cell-mediated anemia

cytotoxicity (ADCC)



• Antibody serves as an opsonin;

phagocytic cells with FcR or C3bR

bind and phagocytose coated cells

Hemolytic disease of newborns

• Drug-induced hemolytic anemia



• Antibiotics can adsorb to RBC membrane proteins and

form hapten-carrier like complexes



• Antibodies can be formed to these complexes and

stimulate the lysis of the RBCs leading to anemia

Hypersen III



• Immune complex-mediated hypersensitivity





• Antigen-antibody complexes facilitate clearance by

phagocytosis



• Large amounts of immune complexes can result in

enhanced immune response leading to tissue

damage

• Localized reaction, Arthus reaction,

develop when complement is

activated



• C3a, C4a, C5a cause localized mast

cell degranulation and increased

vascular permeability





• C3a, C5a, C5b67 are chemotactic

factors for neutrophils





• Tissue damage is due to the release

of lytic enzymes by neutrophils as

they phagocytose the immune

complex





• Response to insect bites (rapid type I

followed by slower type III)





• Type III: pronounced edema and

erythema

• Immune complex-mediated

hypersensitivity



• Generalized immune response



• Large amounts of antigen

enter the blood



• Formation of circulating

immune complexes



• Generation of antibodies to

foreign serum proteins



• Development of serum

sickness, autoimmune disease,

drug reactions, infectious

disease

Hypersen IV



• Initiated by cytokines secreted by subgroups of TH

cells



• Characteristics



• delayed onset of response



• large influx of macrophages and Langerhans cells



• Necessary and detrimental tissue damage

Primary and Secondary IR

Autoimmunity

Immunization

Complement

Immunity to infections

Bacterial infections

Viral infections

APC and spleen, lymph node

MHC class I/CD8 MHC class II/CD4



Endogeneous Ag Exsogeneous Ag

Spleen or lymph node

Cytokines

• Therapeutic use of

cytokines



• Organ transplantion



• Inflammation



• Cancer therapy



• Infectious disease



• Allergy



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