CH9: alteration immunity, inflammation

allergy

exaggerated response against environmental antigen

autoimmunity

misdirected response against host own cell

immune system attack self-antigen

alloimmunity

directed against beneficial foreign tissue

foreign tissue

altered immune responses

allergy

autoimmunity

alloimmunity

can be serious or life-threatening

hypersensitivity

altered immunologic response to antigen, disease or damage to host

immediate hypersensitivity reaction

delayed hypersensitivity reaction

immediate hypersensitivity reaction

reaction occur within min to few hour

anaphylaxis: systemic or cutaneous

delayed hypersensitivity reaction

reaction take several hour to appear

anaphylaxis

dev min after exposure

immediate hypersensitivity

• itch

• erythema

• headache

• vascular collapse

common triggers: peanuts, shellfish, eggs, bee stings

hypersensitivity immune mechanism

type I: IgE-mediated

type II: tissue-specific reaction, cytotoxic

type III: immune complex-mediated, immune complex

type IV: cell-mediated, delayed

Type I hypersensitivity

IgE mediated

IgE antibodies

mast cell activation → histamine release

H1/H2 receptor increase chemotactic activity

type I manifestation

H1: bronchial constriction, edema, vasodilation

H2: increase gastric secretion, decrease release histamine from mast cell/basophils

• Skin: hives (urticaria), itching, angioedema

• Respiratory: asthma, bronchospasm, laryngeal edema

• GI: nausea, vomiting, diarrhea

• Severe form = Anaphylaxis

type II hypersensitivity

specific cell or tissue is target of immune response

cytotoxic (tissue-specific)

type II 5 mechanisms

1. cell destroyed by antibodies/complement

2. cell destruction occur by phagocytosis

3. neutrophil release granules

4. antibody dependent cell-mediated cytotoxicity present

5. target cell malfunction

type III hypersensitivity

antigen-antibody complex mediated

not organ specific

activates complement + neutrophils

type III immune complex clearance

large: macrophages

small: renal clearance

intermediate: deposited in tissue, cause problem

immune complex disease

variety symptoms

remission or exacerbation occur

• serum sickness

• arthus reaction

type IV hypersensitivity

mediated by T lymphocyte or cell mediated

delayed response 24-72 hr

• Cytotoxic T cells kill target cells

• Helper T cells release cytokines

• Macrophages cause tissue damage

antigenic target: allergy

• Environmental antigens (pollens, foods, animal dander)

• Requires sensitization

• Genetic predisposition = Atopic

IgG-blocking antibodies

food/skin test, lab test IgE

antigenic target: type IV

hapten react w/normal self-protein in skin

allergic contact dematitis

antigenic target: type II/III

hapten bind to surface of cell and elicit an IgG or IgM response

antigenic target: autoimmunity

• Loss of self-tolerance

• Immune system attacks self

• Familial/genetic association

antigenic target: alloimmunity

• Reaction against same-species tissue

• Transplants, transfusions

• Neonatal alloimmunity

autoimmune disease: systemic lupus erythematosus (SLE)

no cure

• Chronic, multisystem inflammatory disease

• More common in females

treatment: NSAIDs, steroids, Antimalarials, Antimalarials

antibodies against: DNA, RBC, platelets, phospholipids

transfusion reaction

alloimmune reaction

ABO system

A/B codominant

O blood type: universal

AB blood type: universal recipient

Rh system

• Rh+ has D antigen

• Rh− lacks D antigen, - mother = + fetus

• Rh incompatibility → hemolytic disease of newborn

Rho(D) immune globulin

hemolytic disease of newborn

Rh- mother gives to birth to Rh+ infant

warm autoimmune hemolytic anemia

IgG antibodies react w/erythrocyte at normal body temp

cold autoimmune hemolytic anemia

IgM autoantibodies react w/erythrocyte in cooler portion of body

graft rejection

alloimmune reaction

• Hyperacute: Immediate, preformed antibodies

• Acute: Days–weeks, T-cell mediated

• Chronic: Months–years, gradual damage

deficiencies immunity

impaired function T/B, phagocyte, complement

primary (congenital): genetic, SCID, DiGeorge

secondary (acquired): cause by other illnesses, chemotherapy

primary immune deficiencies

B/T lymphocyte deficient

antibody deficient

immune dysregulation

phagocytic defect

innate immunity defect

complement defect

combined deficiencies

severe combined immunodeficiency (SCID)

bare lymphocyte deficiency

wiskott-aldrich syndrome

DiGeorge syndrome

severe combined immunodeficiency (SCID)

few detectible lymphocyte

underdev thymus

absent/reduce IgM/IgA

bare lymphocyte deficiency

adequate B/T cell

inability to produce MHC I/II

wiskott-aldrich syndrome

depressed IgM production w/bleeding

DiGeorge syndrome

thymic aplasia or hypoplasia

diminish parathyroid dev (T-cell/calcium deficiency)

hypogammaglobulinemia or agammaglobulinemia

bruton agammaglobulinemia: severe

autosomal agammaglobulinemia: mutation IgM

X-linked hyper-IgM syndrome: defective class switch

activation-induced cytidine deaminase deficiency (AICD): DNA defect inhibit

IgG subclass deficiency: pneumonia

IgA deficiency: does not produce

common variable immunodeficiency: common

phagocyte defect

severe congenital neutropenia: prone to bacterial infection, cyclic neutropenia

leukocyte adhesion deficiency type I/II: mutation occur

chronic granulomatous disease: chronic granulomatous disease

myeloperoxidase deficiency: complete/partial deficiency myeloperoxidase

chronic mucocutaneous candidiasis

primary defect T lymphocyte in response to specific infectious agent

candida albicans yeast

autoinflammatory disorder: familial mediterranean fever

eastern mediterranean population

uncontrolled release IL-1B

fever,skin rash

complement deficiencies

C3: severe, major opsonin

mannose-binding lectin deficiency: prone to yeast

properdin deficiency: meningococcal infection, X-linked

factor I/H deficiency: destroy C3

C5-C9: prone to neisseria infection

secondary immune deficiency

acquired deficiencies

dietary insufficiencies

metabolic disease

genetic syndrome

malignancies

infection

medical treatment

replacement therapies for immune deficiencies

gamma-globulin therapy

transplantation or transfusion

treatment w/soluble immune modulator

gene therapy

evaluation and care of those w/immune deficiency

complete WBC w/ WBC differential

quantitive determination immunoglobulin

assay for total complement skin test