Immunity

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Immunity Abnormal Responses

• Pathophysiology

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• Diseases to be discussed
• Tissue rejection
• Includes Organ transplant rejection
• Hypersensitivity reactions
• These are hyperactive responses of the immune
  system
• Called allergies
• Autoimmune reactions
• A misdirected immune response
• Immunodeficiency
• A deficient immune response

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Review of Immune System

• Nonspecific immunity
• Barriers
• Fluids
• Inflammatory reaction
• Phagocytosis
• Antimicrobial substances
• See next slide
• Specific immunity
• Immune response
• Humoral
• Cellular
• Acquired immunity
• Natural
• Active passive
• Artificial
• Active passive

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• Non-specific Immunity System Molecules
• Complement system membrane attack video
• Group of inactive plasma proteins, part of
  non-specific immunity
• Especially active against invading bacteria
• When activated, system compliments action of
  antibodies by
• Destruction of target cell membranes
• Attracts phagocytes (chemotaxis)
• Stimulates enhances phagocytosis
• Stimulates inflammation
• Activation occurs via
• Compliment binding to IgM or IgG antibody-
  antigen complex
• Compliment attaching to foreign materials, e.g.
  bacterial cell wall
• Interferon Interferon video clip
• Especially active against viruses
• Small proteins released by lymphocytes
  macrophages (primarily T-lymphocytes) when these
  cells activated by viral antigens
• Interferons do 2 basic things
• Bind to normal body cell with virus via second
  messenger stimulate the production of antiviral
  proteins in cytoplasm which stop viral
  replication
• Act as cytokines to stimulate production of more
  macrophages lymphocytes

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Specific ImmunityThe Immune Response

• Step I
• Macrophages alert lymphocytes
• Step II
• Humoral immune response
• Step III
• Cellular immune response

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Summary of Normal Specific Immune ResponseNormal
specific immune response can be either Primary or
Secondary
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Primary Secondary Immune Responses

• Secondary response when repeat exposure to same
  antigen occurs
• Deals primarily with memory cells (both B T)
• Memory B antibodies
• Memory T T cells
• Helper Killer

• Primary response when person first exposed to
  antigen

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• Antibodies ---- Immunoglobulins
• General structure Y 2 light chains 2 heavy
  chains
• Variable region--- binds to antigen
• Constant region --- attaches to macrophage
• 5 different types of constant regions
• MADGE all monomers, but M pentamer A
  dimer
• The constant regions have no effect on the
  specificity of the antibody

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• 5 types of immunoglobulins produced by plasma
  cells
• IgM
• First secreted after arrival of antigen
• In monomer form, can act as receptor on cell
  membrane
• Usually in pentamer form, thus large can cause
  agglutination
• Activates compliment
• Present early in the course of infection then
  falls as IgG levels rise
• IgG
• Most numerous of circulating antibodies (75)
• Called gamma globulin
• Effective against all pathogens most toxins
• Can cross placenta
• Is key antibody in primary secondary immune
  response
• Can activate compliment
• IgA
• In epithelium, thus in secretions (mucus, tears,
  saliva, colostrum, etc.)
• Prevents attachment of viruses bacteria to
  epithelial surfaces

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• 5 types of immunoglobulins produced by plasma
  cells
• IgE
• Attached to basophils mast cells
• When antigen attaches, these cells release
  histamine
• Thus, they involved in allergic reactions
  (hypersensitivity rx)
• Called troublemaker antibody since they cause
  allergic reactions when exposed to antigen
• IgD
• Always attached to B lymphocyte
• Can activate B lymphocyte
• May be important in causing B cell to become
  either plasma cell or memory cell

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• Antigen presenting proteins the processing of
  the antigen
• Those proteins made by the cell that are
  incorporated into the cell membrane hold or
  present foreign antigenic material that has
  gotten into the cell
• These are usually glycoproteins everybody has
  different ones
• Controlled by genes on chromosome 6 in region
  called MHC
• MHC major histocompatability complex
• Antigen presenting proteins also called MHC
  proteins
• Used to be called HLA (human leukocyte antigens)
• In immune system key cell is macrophage --- it is
  an antigen presenting cell
• 2 classes of MHC proteins
• (1) MHC class I --- made continuously by all
  nucleated cells
• For viral antigens normal peptides made by cell
• (2) MHC class II --- made only by macrophages
  lymphocytes when cell is
  processing antigens
• For antigenic fragments produced by lysosome
• Activation of lymphocytes
• Antigen presenting proteins foreign antigen
  -------- fit into receptor proteins in cell
  membrane of cell that needs activation
• Recognition proteins
• Those in cell membrane that are unique to that
  individual, thus name tags
• These are the same as MHC proteins

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antigen presenting video
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Tissue Organ Transplant Rejection

• When the immune system of the individual responds
  to the HLAs in foreign tissue
• Remember that HLAs MHC proteins
• Mechanism
• type IV cell-mediated hypersensitivity reaction
• Humoral response (antibody production)
• To decrease risk
• HLA match is excellent
• Donor is living
• Use of immunosuppressive drugs
• Side effects --- opportunistic infections

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Hypersensitivity Reactions

• Types
• Type I hypersensitivity---- allergy
• Mech IgE bound to mast cell release of
  histamine and chemical mediators
• Person exposed to allergen causes B cells to make
  IgE antibodies
• These IgE attach to mast cells make them
  sensitized
• Upon re-exposure get An IgE mast cell
  releases chemical mediators
• Sx depend on where the sensitized mast cells
  located
• Hay fever (allergic rhinitis)
• Food allergies
• Atopic dermatitis(eczema)
• Atopic means runs in families, thus genetic
  component
• Asthma
• Anaphylaxis severe allergic reaction
• Mech large amounts of chemical mediators
  released from mast cells
• Can get C-V collapse severe bronco-constriction

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• Type I --- allergy

• Type I --- anaphylaxis reaction

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• Type II hypersensitivity --- cytotoxic
  hypersensitivity
• Mech
• The antigen is on the cell membrane
• Circulating IgG react with the antigen get cell
  destruction
• Examples
• ABO incompatibility
• Rh incompatibility

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• Type III --- immune complex hypersensitivity
• Mech
• Antigen-antibody complex deposits in tissue
• Tissue is frequently blood vessel walls
• Complement is activated
• Sx inflammation tissue destruction
• Examples
• Glomerulonephritis
• Rheumatoid arthritis
• Arthus reaction localized inflammation tissue
  necrosis
• Seen in valley feverin humans

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• Type IV ---- Cell- mediated or delayed
  hypersensitivity
• Mech
• Antigen binds to T-lymphocyte
• The sensitized T cell releases lymphokines
• The sensitized T cell begins the immune response
• The lymphokines release chemical mediators that
  destroy the antigen
• Examples
• Skin tests
• Contact dermatitis
• Poison ivy
• Organ transplant rejection
• Occurs after first exposure
• Dont need sensitization
• Step in Type I

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Autoimmune Disorders

• Immune system forms antibodies to self antigens
• Remember that these are MHC-proteins
• Genetic factor involved in auto immune disease
• Systemic(SLE) localized diseases (Hashimotos
  disease)
• Systemic Lupus Erythematosus

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• SLE
• General
• Primarily women age 20-40
• Butterfly rash face of wolf (lupo)
• Course remissions exacerbations
• Pathophys
• Get circulating anti-DNA antibodies anti-nuclear
  antibodies(ANA)
• Immune complexes deposited in connective tissue
  anywhere in body
• Get inflammation necrosis
• Vasculitis gives ischemia
• Sx
• Initially skin rash, joint inflammation(polyarthr
  itis)
• Pleuritis
• Carditis
• Raynaulds phenomenon
• Glomerulonephritis
• Dx
• LE prep
• ANA

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SLE (Systemic Lupus Erythematosus)

• General
• Primarily women age 20-40
• Butterfly rash face of wolf (lupo)
• Course remissions exacerbations
• Pathophys
• Get circulating anti-DNA antibodies anti-nuclear
  antibodies(ANA)
• Immune complexes deposited in connective tissue
  anywhere in body
• Type III hypersensitivity Rx
• Get inflammation necrosis
• Bone marrow depression
• Esp. thrombocytopenia
• Vasculitis gives ischemia
• Sx
• Initially skin rash, joint inflammation(polyarthr
  itis)
• Pleuritis
• Carditis
• Raynaulds phenomenon
• Glomerulonephritis

• Dx
• LE prep
• ANA
• Tx
• Steroids
• Avoid sun
• Px
• Was 5-10 years
• Currently much better

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Immunodeficiency

• Primary immunodeficiency disorders congenital
  and/or genetic
• Secondary immunodeficiency disorders those
  acquired
• Causes
• Immunosuppressive therapy
• Chemo radiation cancer treatment
• HIV infection
• Use of corticosteroids
• Effects
• Opportunistic infections
• Increase of certain cancers, especially
  non-Hodgkins lymphoma

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AIDS (Acquired Immunodeficiency Syndrome)

• Etiology HIV virus
• Retrovirus (RNA)
• Antibodies appear after initial infection
• Avg time 4-8 wks
• May take as long as 6 months
• Transmission
• Via blood body fluids
• Exception saliva
• Virus is fragile cannot live outside body
• Not by casual contact
• Tests
• ELISA(enzyme-linked immunoassay)
• Western blot
• CD4 counts

• Pathophys
• Virus has predilection for
• Helper T lymphocytes
• Macrophages
• CNS cells
• Course of HIV infection (see next slide)
• Initial phase like URI
• May last longer than usual cold
• Latent phase up to 10 years
• Active disease --- AIDS
• Usually begins with generalized lymphadenopathy
• G-I effects esp diarrhea with cachexia
• Opportunistic infections
• HIV encephalopathy
• Cancers

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Stages in development of AIDS
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AIDS (Acquired Immunodeficiency Syndrome)

• HIV encephalopathy
• Called AIDS dementia
• Can end with seizures coma
• Women with HIV
• AZT pregnancy
• Tx
• Reverse transcriptase inhibitors
• Protease inhibitors
• Viral integrase inhibitors
• Tx opportunistic infections

• Opportunistic infections
• TB
• PCP(pneumocystis carinii pneumonia) fungus
• Frequent cause of death in AIDS
• Toxoplasmosis
• Candidiasis
• Herpes
• Varicella
• Cytomegalovirus retinitis
• Necrotizing periodontal disease
• Opportunistic cancers
• Kaposis sarcoma
• Non-Hodgkins lymphoma

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