Immunology II Flashcards
Define: hypersensitivity rxn
- Exaggerated, inappropriate immunologic rxn that is harmful to the host
- Subsequent exposure
Define: sensitivity
1st exposure to antigen w/ immune response (antibody)
Type I action
- 1st exposure to antigen –> IgE formation
- IgE binds to mast cells & basophils
- Subsequent exposure – > antigen binds to IgE
- Degranulation of mast cells
- Release of mediators (histamine)
Type I result
- Increased vascular permeability
- Edema
- SM contraction
Type I timing
Minutes
Type I manifestations
- Edema
- Erythema
- Itching
- Urticaria
- Eczema
- Rhinitis
- Conjunctivitis
- Asthma
- Systemic anaphylaxis
- Food/drug allergies
- Hay fever
Allergic response
- During sensitization, APC presents allergen presents to Th2 cell, which helps B cell become a plasma cell.
- Plasma cells produce IgE, which binds to mast cells.
- When allergen returns, mast cells release histamine
- Th2 cells release chemicals that attract inflammatory cells
Allergic response results in what?
Allergy sx
- Sneezing
- Mucus, runny nose
- Swelling
- Itching
- Coughing, wheezing
What is the effect of histamine?
- Vasodilation
- Increased capillary permeability
- SM contraction
What is the emergency concern of anaphylaxis?
- Airway
- Hypotension
- Shock
What is the emergency tx for anaphylaxis?
- Epinephrine
- Antihistamine
- Steroid
Anaphylaxis prevention
- Antihistamine
- H2 blocker
- Avoid allergen
- Immunosuppression therapy w/ allergy shots
What is the rationale of desensitization?
Tiny amount of antigen over long period of time to blunt rxn
What infections may exacerbate asthma?
- Flu
- PNA
Most common food allergies (90%)
- Milk
- Egg
- Fish (bass, flounder, cod)
- Shellfish (crab, lobster, shrimp)
- Tree nuts (almonds, pecans, walnuts)
- Wheat
- Peanuts
- Soybeans
*Also consider fruits, preservatives, dyes.
Type I hypersensitivity common presentation
- Facial edema
- Systemic histamine release in anaphylaxis:
˚ Hypotension
˚ Nausea
˚ Hives
˚ Swollen hands/feet
Type II (cytotoxic) hypersensitivity rxn
- Antibody mediated cytotoxic rxn
- Antigens on cells or in ECM (endogenous or exogenously absorbed)
Type II action
Antigens on cell surface combine w/ IgG antibodies –> complement-mediated lysis of cells
Type II time of onset
Hours to days
Type II manifestations
- Hemolytic anemia
- Neutropenia
- Thrombocytopenia
- ABO transfusion rxns
- Rh incompatibility (erythroblastosis fetalis, hemolytic disease of the newborn)
- Rheumatic fever
- Goodpasture’s syndrome
Hemolytic anemia (Type II)
- Antibody attaches to antigen on RBC
- Complement mediated lysis via MAC
- Complement attracts phagocytes
Type III (Immune complex) hypersensitivity
- Antigen–antibody immune complexes are deposited in tissues –> inflammatory response
- Complement is activated & PMN cells are attracted to the site –> release of lysosomal enzymes –> tissue damage
Type III time of onset
2-3 wks
Type III manifestations
- SLE
- RA
- Poststreptococcal glomerulonephritis
- IgA nephropathy
- Serum sickness
- Hypersensitivity pneumonitis (farmer’s lung)
SLE (Type III)
- Antibodies formed to DNA & nucleus
- Antibodies form immune complexes that activate complement –> production of C5a –> attracts neutrophils –> release enzymes –> damage tissue
RA (Type III)
- Serum & synovial fluid contain “rheumatoid factor” (IgM & IgG antibodies that bind to the Fc fragment IgG)
- Deposits of immune complexes (containing the normal IgG & Rh) on synovial membranes & in blood vessels
- Activate complement & attract PMN cells –> inflammation.
- Pts have high titers of Rh & low titers of complement in serum (esp. during periods when disease is most active)
Type IV: Delayed (Cell-mediated) hypersensitivity
- T lymphocytes, activated/sensitized by an antigen, release lymphokines upon 2nd contact w/ same antigen
- Lymphokines induce inflammation & activate macrophages –> release of inflammatory mediators.
Type IV time of onset
2-3 days
Type IV manifestations
- Contact dermatitis
- Poison oak/ivy
- TB skin test rxn
- Drug rash
- Stevens-Johnson syndrome
- Toxic epidermal necrolysis
- Erythema multiforme
Type IV continued
- Macrophage ingests antigen, processes it, & presents an epitope on its surface in association w/ class II MHC
- Helper T (Th-1) cell is activated & produces gamma interferon –> activates macrophages
- These 2 cells mediate delayed hypersensitivity
Hereditary angioedema
- Congenital immunodeficiency (deficiency of C1 protease inhibitor, autosomal dominant)
- Excess C3a, C4a, C5a
Hereditary angioedema result
Capillary permeability & edema
Hereditary angioedema dx
- Family hx
- Lack of pruritis & urticarial lesions
- Recurrent abdominal colic &/or laryngeal edema
- Labs: decreased C1 inhibitor levels (or decreased fxn, or mutation in C1 inhibitor gene altering synthesis/fxn)
Fxn of immune system
Provide a protective response against infective organisms & foreign cells, while avoiding damage to self
Markers of self
- Distinctive surface proteins that identify “self”
- Able to coexist w/ immune system
- Unique markers on human cells are the MHC proteins (type I = all cells, type II = specialized cells)
Markers of non-self
- Non-self substance (antigen) can trigger the immune system
- Epitope: area on the antigen that triggers a response
- Ex: transplanted tissues are recognized as foreign & attract antibodies
Self-antigens
Mechanisms for avoiding damage to self
- Sequestration
- Tolerance of relevant T or B cells
- Regulatory cells
What is an autoimmune disease?
A trigger interferes w/ normal mechanisms protecting antigens against immune response –> tissue injury
Types of autoimmune triggers
- Exogenous
- Endogenous
- Molecular mimicry (pathogen derived antigen)
Autoimmunity criteria
- Autoantibodies
- Self-reactive T lymphocytes
- Imbalance btwn T & B cell & regulatory factors
Etiologies of autoimmune disease
- Genetic susceptibility
- Environmental immune stimulants
- Infectious agents
- Loss of T regulatory cells
- Decreased clearance of apoptotic material
- Antibodies that react w/ apoptotic material
Graves disease - Environmental & genetic factors
- Stress
- Smoking (minor risk, but major risk for opthalmopathy)
- Sudden increased iodine intake
- Post-partum
Graves disease
- Autoantibody stimulation of TSH receptor (TSI)
- Thyroid associated ophthalmopathy (T cells activate cytokine infiltration)
Rheumatic fever
- Autoimmune rxn to infection w/ group A streptococcus
- Molecular mimicry
Rheumatic fever susceptibility
- Inherited
- Human leukocyte antigen class II alleles – some associated w/ susceptibility & some are protective
- Cardiac valve damage = rheumatic heart disease
Myasthenia Gravis
- Autoantibody blocking/inactivation of alpha-chain of nicotinic acetylcholine receptor at neuromuscular junctions
Abnormalities of the thymus (Myasthenia Gravis)
- Hyperplastic
- Tumors
- Muscle-like cells within thymus (have AChRs on surface - may be source of auto antigen triggering)
Myasthenia Gravis antibodies
Anti-AChR
- Increases receptor turnover
- Damage to postsynaptic muscle membrane by antibody & complement
- Blockage of AChR active site that normally binds Ach
SLE
- Type III
- Immune complex formation targeting DNA
- Genetic susceptibility & environmental factors –> abnormal immune response
- Immune cell activation –> sustained autoantibody & immune complex production, activation of complement, release of chemical mediators
SLE antibodies
Anti-dsDNA, anti-Smith
SLE chronic inflammation
Leads to irreversible tissue damage
Type I DM genetic susceptibility
Genes that code for MHC class II molecules
Type I DM environmental factors
- Perinatal
- Viruses
- Dietary
Type I DM autoantibodies
- Insulin
- Islet cell
Type I DM destruction of pancreatic cells
Caused by T cell cytokine production and cytotoxicity
Rheumatoid arthritis
- Type III
- Genetic factors
- Pro-inflammatory cytokines
RA environmental factors
- Tobacco smoke exposure
- Exposure to silicone dust & mineral oil
RA autoantibodies
- Rheumatoid factor
- Anti-CCP antibodies
Multiple sclerosis
- Genetic susceptibility
- Pro-inflammatory autoimmune response –> destruction of CNS myelin (both T & B cell involvement)
Immunizations
Exploit adaptive immune response
- Uninfected individuals given controlled infection or exposed to antigen that elicits an immune response
- When exposed to pathogen in environment, memory T & B cells mount immune response before pathogen can spread
Passive immunity
Antibody transferred from immune individual to nonimmune individual
Advantage & disadvantage of passive immunity
- Advantage: immediate availability
- Disadvantage: short duration (months)
Active immunity
- Artificial antigens administered to elicit controlled immune response
- Mediators: Antibody and T cells
Active immunity: Advantage & disadvantage
- Advantage: long duration
- Disadvantage: Slow onset
Live attenuated vaccines
- Weakened form of virus
- Antigens stimulate immune response
- Must be refrigerated
- Possible to become virulent again if mutates in host (rare)
- Not for immune compromised or pregnancy
Examples of live attenuated vaccines
Measles Mumps Rubella Varicella Rotavirus Influenza
Inactivated vaccines
- Pathogens killed – isolates antigenic material
- Freeze-dried, don’t require refrigeration
- Induce weaker immune response
- Need multiple doses to sustain immunity
Examples of inactivated vaccines
Poliovirus
Hep A
Japanese encephalitis
Subunit vaccine
- Use component of the pathogen as vaccine antigen to mimic exposure
- Weaker immune response than live attenuated
Recombinant subunit vaccine
Antigens manufactured via recombinant DNA technology
Polysaccharide subunit vaccine
Utilize polysaccharide antigens
Surface protein subunit
Utilize purified proteins from the pathogen
Toxoids
Inactivated or killed toxins used to elicit immune response –> antibodies that can neutralize toxins (Diphtheria)
Conjugate subunit vaccine
- Technology binds polysaccharide from bacterial capsule to a carrier protein
- This antigen combo induces long-term protection
Conjugate subunit vaccine examples
Hib, Pneumococcal (PCV), meningococcal
