Immune System Disorders

Immune Disorders

n    Result due to malfunction of immune system

n    Can lead to

n   Hypersensitivity

n  Inappropriate immune response

n   Immunodeficiency

n  Inadequate immune response

HYPERSENSITIVITY

n    Response to antigens (allergens) leading to damage

n    Individual sensitized by allergen and allergic response occurs after second exposure

n    Four types

n   Anaphylactic

n   Cytotoxic

n   Immune-complex

n   Cell-mediated (or delayed-type)

Type I – Anaphylactic Hypersensitivity
 

n    Less than 30 minutes to react

n    Responses can be local or systemic

n    IgE attach to mast or basophil cells (granulated); Antigen binds to two adjacent IgE

n   Degranulation and release of mediators

n   Possible Responses

n  Increased permeability and dilation of capillaries

n  Increased mucous secretion

n  Smooth muscle contractions or wheezing

n  Chemotactic response that signals neutrophils and eosinophils

Systemic Anaphylaxis

n    Anaphylactic shock

n    Usually by injection, insect stings or penicillin

n    Dilation of blood vessels and decrease in BP which may result in circulatory collapse and death

n    Treatment with epinephrine

Localized Anaphylaxis

n    Associated with food or pollen

n    Hay fever, asthma, hives, rash, etc.

n    Ex. upper respiratory:  sneezing, watery eyes, itching

n    Ex. lower respiratory:  asthma

n    Ex. digestive tract:  usually hives and may become systemic

n   Peanut and egg allergies

Prevention of Anaphylaxis

n     Skin tests to determine what allergies a person has

n   Wheal

n     Avoidance

n     Desensitization

n   Specific amount of antigen (small amount delivered in many doses) to illicit IgG response to neutralize antigen before IgE is called

Type II - Cytotoxic Reactions

n    “Antigenic cell” lysed

n   Antigen= foreign cells or self cells coated with drugs

n    IgG and IgM combine with antigen and a complement reaction causes cytolysis

n    5-12 hours after 2^nd exposure

n    EX. ABO or Rh antigens, incompatible transfusions (RBC lysis)

Blood Types – Fig 19.2

Rh factor – Fig 19.4

n     Named for Rhesis monkey

n     85% of population has it

n     A person is classified as + or – for the Rh antigen

n     Rh –  people make antibody for Rh after initial exposure (i.e. may be from transfusion or from Rh + baby across the placenta)

n   Allergic response if exposed again

n     Rh + people do not make antibody for Rh.

Drug Induced Cytotoxic Reactions

n    Quinine (used to be used to treat malaria)

n   Binds to platelets (hapten)

n   IgG antibodies produced

n  Antibodies bind with platelet and complement

n  Platelets destroyedàhemorrhaging

n  Purple spotsàthrombocytopenic purpura

Type III - Immune Complex Reactions
 

n    Antibodies against soluble antigens circulating in blood

n    Immune complex (Ag-Ab) deposited in organs (inflammation)

n   Involves IgG and response occurs in 3-8 hours

n   Requires a certain ratio of Ag:Ab

n   When Ab in excessàcomplement fixingàphagocytosisàattracts neutrophils

n   When complex trapped in basement membrane the neutrophils cause vessel damage

n   Ex. Glomerulonephritis

Type IV - Cell-Mediated Reactions
 

n    Delayed reactions (24-48 hours)

n    Due to T cells

n    Antigens usually bound to tissue cells first

n    1^st exposure: Phagocytosis by macrophage then presented to T cell receptoràT cell proliferation

n    2^nd exposure: Memory cells activate T cells which release cytokinesàattract macrophages and inflammation occurs

n    Ex. Poison ivy, latex (contact dermatitis), TB test

Autoimmune Disease

n    Loss of self-tolerance

n    Normally T cells pass through thymus and those specific for self antigens are deleted (clonal deletion)

n    Four types

n   Autoimmunity

n   Cytotoxic

n   Immune Complex

n   Cell-Mediated

Type I Autoimmunity

n    Most genetic diseases

n    Hepatitis C virus can cause autoimmune disease

n   Antibodies made for Hep C end up attacking liver cells

Type  II  - Cytotoxic Autoimmune

n    Graves Disease

n   Thyroid gland is overstimulated by antibodies that bind to thyroid gland cells

n  Enlarged thyroid gland; overproduction of thyroid hormones; bulging eyes and goiter

Type III – Immune Complex Autoimmune

n    Rheumatoid arthritis

n   IgM bound to Fc region of IgG (rheumatoid factor) and deposited in joints

n  Severe inflammation from immune complex in joints

Type IV – Cell-Mediated Autoimmune

n    Diabetes mellitus

n   T cells help destroy Islets of Langerhans

n  Islets cells produce insulin

n  Without insulin a diabetic cannot metabolize sugar and sugar accumulates in blood

n   This causes organ damage over long term

n  Type I diabetics must take insulin injections and it is often difficult to determine how much insulin to take under various circumstances.

Acquired Immunodeficiency Syndrome (AIDS)

n1981: In United States, cluster of Pneumocystis and Kaposi's sarcoma in young homosexual men discovered. The men showed loss of immune function.

n1983: Discovery of virus causing loss of immune function.

The Origin of  AIDS

nCrossed the species barrier into humans in Africa in the 1930s.

nPatient who died in 1959 in Congo is the oldest known case.

nSpread in Africa as a result of urbanization.

nSpread world-wide through modern transportation and unsafe sexual practices.

nNorwegian sailor who died in 1976 is the first known case in Western world.

Acquired Immunodeficiency Syndrome (AIDS)

nHuman Immunodeficiency Virus

nRetrovirus

nTwo identical strands of RNA, reverse transcriptase, and phospholipid envelope containing gp120 glycoprotein*

nMainly infects helper T cells, macrophages, and dendritic cells

nAttaches to CD4 receptors and chemokine co-receptors (receptors found on T cells)

nEntry into host cell, release of RNA, reverse transcription of RNA into DNA, and integration of DNA into host chromosome

Reasons why antibodies fail to inhibit HIV

n    HIV structure:  gp120 makes it difficult for antibodies to bind to virus surface

n    Latent virus hidden inside host cells

n    Cell-cell fusion method of infecting new cells

n    Retrovirus evolution causing rapid antigenic changes

n   Lack proofreading capability

n   High mutation rate

AIDS

n    AIDS determined by number of CD4 T helper cells in blood

n   Normally 600-1000/mm³ infected individuals have 200 or less

n    Cells have a shortened life and body can’t produce them fast enough

n    Drugs used to suppress numbers of HIV so body can produce and maintain T cells

Clades (Subtypes) of HIV

n  HIV-1

n  M (main)

n  A to D, F to H, J, and K

n  O (outlier)

n  N (non M or O)

Clades (Subtypes) of HIV

n  Clade B

n  North and South America and Europe

n  Clade C (half of all HIV infections)

n  Central Africa down to South Africa

n  India and southeast Asia

n  Parts of China

n  Clade E

n  Southeast Asia

The Stages of HIV Infection

n  Phase 1: Asymptomatic or chronic lymphadenopathy

n  Phase 2: Symptomatic; early indications of immune failure

n  Phase 3: AIDS indicator conditions

The Progression of HIV Infection

HIV Transmission

nHIV survives 6 hours outside a cell

nHIV survives less than 1.5 days inside a cell

nInfected body fluids transmit HIV via

nSexual contact

nBreast milk

nTransplacental infection of fetus

nBlood-contaminated needles

nOrgan transplants

nArtificial insemination

nBlood transfusion

Modes of HIV Transmission

AIDS Worldwide

Prevention of AIDS

nEducation

nUse of condoms and sterile needles.

nHealth care workers use Universal Precautions

nWear gloves, gowns, masks, and goggles.

nDo not recap needles.

nRisk of infection from infected needlestick injury is 0.3%.

Vaccine Difficulties

n  Mutation rate

n  Clades

n  Antibody-binding sites “hidden”

n  Variety of transmission routes

n  No suitable experimental host

n  Proviruses

n  Latent viruses

Chemotherapy

n  Nucleoside analogs (AZT) that terminate synthesis of viral DNA (and also human DNA)

n  Fusion inhibitors

n  Nucleoside reverse transcriptase inhibitors