CH 18 - Immunological Disorders Flashcards
Allergy
(definition)
A damaging immune response to a typically harmless environmental antigen (allergen)
Autoimmune Disease
(definition)
Damaging reaction of the immune system against “self” antigens
Delayed-type hypersensitivity
(definition)
Exaggerated immune response of antigen-specific T cells
Desensitization
(definition)
Allergy treatment that induces IgG production by gradual exposure to small amounts of allergen
IgG competes with IgE
Hypersensitivity
(definition)
Exaggerated immune response that damages tissue
Immune complex
(definition)
Combination of antibody & soluble antigen capable of triggering the classical pathway of complement system activation
Immunodeficiency
(definition)
Condition in which the immune system does not provide an adequate response, leaving a person vulnerable to infection
Systemic anaphylaxis
(definition)
Potentially life-threatening immediate hypersensitivity reaction caused by IgE attached to circulating basophils
Hypersensitivities:
Categorization
Categorized according to which parts of the immune system are involved & how quickly response occurs
Type I - Imediate IgE-mediated
Type II - Cytotoxic
Type III - Immune complex-mediated
Type IV - Delayed cell-mediated
Type I Hyper Sensitivities
Immediate IgE-mediated
- Allergic reactions
Driven by B cells
- IgE Abs bind to mast cells & basophils
- Ag binds to cells fixed with IgE Ab
(cross-linking of IgE)
- Degranulation (initiates immune reaction)
Immediate reaction
- Within mins of exposure
Hives, hay fever, anaphylaxis
Type II Hypersensitivities
Cytotoxic
- Tissue incompatibility
Driven by B cells
Complement-fixing Abs react with cell surface Ags
- Cause cell injury/death
Cells destroyed through complement fixation & Ab-dependent cellular cytotoxicity (ADCC)
Transfusion rxns (complement fixation)
Hemolytic disease of newborn (ADCC)
Transfusion Reactions
Transfused antigenically different blood can be lysed by recipient immune cells
- IgM Abs
Type A = alpha-B Abs
Type B = alpha-A Abs
Type O = alpha-B & alpha-A Abs
Type AB = neither
Symptoms:
- Low BP
- Pain
- Nausea
- Vom
Hemolytic Disease of Newborn
Incompatibility of Rh factor between mother & child
- Rh = RBC surface antigen (present if +)
Anti-Rh Abs form in Rh- mother upon delivery of Rh+ infant (mixing blood)
- 1st Rh+ fetus unharmed
- 2nd Rh+ fetus provokes strong secondary immune response
IgG Abs cross placenta & cause extensive damage to fetal RBCs
Prevention = administration of anti-Rh Abs to mother within 72 hrs of birth
- Blocks sensitization phase
- Rhogam
Type III Hypersensitivities
Immune complex-mediated
- Immune complexes = Ag & Ab bound
Form when excess of Ag & Ab in tissue (series of vaccines, horse serum)
- Usually adhere to Fc receptors on cells (removed & destroyed)
Persist in circulation or in sites of formation
- Initiate blood clotting mechanism
- Activate complement (inflammation)
Complexes often deposited in:
- Skin
- Joints
- kidney
Disseminated intravascular coagulation (DIC)
- Clots in small vessels (leaky blood vessels)
- Leads to system failure (dramatic BP drop)
Serum Sickness
Type III hypersensitivity
Immune complex disease caused by passive immunization
- Ab-containing serum from animal injected in humans (treat/prevent disease)
Symptoms manifest within days/weeks following exposure to foreign serum Ags
- Fever
- Weakness
- Generalized vasculitis (redness) with edema
- Inflammation of blood vessels
- Arthritis
- Glomerulonephritis (sometimes)
Type IV Hypersensitivities
Delayed cell-mediated
- Slowly developing response to Ag
- Reaction peaks 2-3 days (after Ag exposure)
Driven by T cells
- Caused by cell-mediated immunity
- Extensive host cell destruction & progressive loss of tissue function (in chronic infections)
Reactions can occur anywhere in body
- Contact dermititis
- Tissue damage
- Rejection of tissue grafts
- Some autoimmune diseases
Tuberculin Skin Test
Type IV hypersensitivity
Introduction of small quantities of protein Ags from tubercle bacillus into skin
+ test = site reddens & gradually thickens (peaks 2-3 days, return after 72 hrs)
T cells release cytokines
- Initiate inflammation that attracts macrophages
- Macrophages release mediators to add to inflammation
Granuloma (tubercle) containing live bacteria forms when macrophage fails to kill
- Result of prolonged DTH response
Contact dermatitis
Type IV hypersensitivity
Small molecules complex with skin proteins
- Internalized by APCs in skin (Langerhans cells), processed, & presented with MHC II
- Causes activation of sensitized Th1 cells
Rash takes few days to develop (T cells must migrate to site)
Ex: poison oak, poison ivy, nickel, cosmetics, hair dyes
Autoimmune Diseases
Body usually recognizes self Ags
- Destroys cells that would destroy self
- Malfunction of immune recognition leads to autoimmunity
May result from reactions to Ags similar to MHC self Ags
May occur after tissue injury
- Self Ags released from injured organ
- AutoAbs form & interact with injured tissue
Spectrum of Autoimmune Diseases
Organ-specific
- Thyroid disease (only affects thyroid)
Widespread response
- Lupus
- Rheumatoid arthritis
- Myasthenia gravis
Lupus
AutoAbs made against nuclear constituents of all body cells
Rheumatoid arthritis
Immune response made against collagen (in joints) & CT
Usually occurs in older people (immune system doesn’t function as well)
Myasthenia gravis
AutoAb-mediated disease
AutoAb to ACh receptor proteins
- Act at NMJ
- Can lead to paralysis
Immunodeficiency Disorders
Body’s inability to make & sustain adequate immune response
2 basic types:
1. Primary/congenital
2. Secondary/acquired
Primary Immunodeficiencies
Inborn
- Genetic defect or developmental abnormality
- Generally rare
- Agammaglobulinemia
- Severe combined immunodeficiency disorder (SCID)
- Selective IgA deficiency
Agammaglobulinemia
Few/no Abs produced
Occurs in 1 in 50,000 people
Severe combined immunodeficiency disorder (SCID)
Neither B nor T cells functional
- Adaptive immune system
Occurs in 1 in 500,000 live births
Selective IgA deficiency
Little/no IgA produced
Most common disorder
- 1 in 333-700 people
People with this condition notice that they get sick more often
(GI & lung illnesses - where IgA normally protects)
Secondary Immunodeficiencies
Result of infection or other stressor
- Environment rather than genetics
- Malignancies, advanced age, infections, immunosuppressive drugs, malnutrition
Depletion of certain cells of immune system
- Syphilis, leprosy, & malaria
- Malignancies of lymphoid system
- AIDS
Syphilis, Leprosy, & Malaria
(Secondary Immunodeficiency)
Affect T cell population & macrophage function
Malignancies of Lymphoid System
(Secondary Immunodeficiency)
Decrease Ab-mediated immunity
AIDS
(Secondary Immunodeficiency)
Destroys helper T cells
Inhibits initiation of cellular & Ab-mediated immunity
Naturally Acquired Immunity
Acquisition of adaptive immunity through natural events
Passive or active
Artificially Acquired Immunity
Mimicking natural events through immunization
Passive or active
Active Immunity
Results from immune response upon exposure to Ag
Develops naturally following illness
Develops artificially after immunization
Passive Immunity
Artificial passive immunity
- Transfer of Abs produced by another person/animal
- Prevents disease before/after likely exposure
Natural passive immunity
- During pregnancy mother’s IgG crosses placenta to infer protection to baby
- During breastfeeding mother’s IgA given to child
Attenuated Vaccines
Weakened form of pathogen
- Generally unable to cause disease
Strain replicates in recipient
- Causes infection with mild/undetectable symptoms
- Results in long-lasting immunity
Most common form of flu vaccine
Attenuated Vaccines:
Advantages
- Single dose usually sufficient to induce long-lasting immunity
- Microbe multiplies in body
- T cell activation
- Continued stimulation of immune system - Vaccine has potential for being spread
- “Disease” could be spread to un-immunized inadvertently
Attenuated Vaccines:
Disadvantages
- Potential to cause disease in immunocompromised
- Pregnant women should avoid
Attenuated Vaccines Currently in Use
- Sabin polio vaccine
- MMR
- Yellow fever
Inactivated Vaccines
Unable to replicate in vaccinated individual (not alive)
Retains immunogenicity of infectious agent
- Immunogenic NOT pathogenic
2 categories:
1. Whole agents
2. Fragments
Inactivated Vaccines:
Whole Agents
Contain killed organisms of inactivated microbe
Does NOT change epitopes
Ex: Influenza & Salk polio
Inactivated Vaccines:
Fragments
Portions of organisms or agents
- Toxins
- Proteins
- Cell wall components
Ex: toxoids, protein subunit vaccines, polysaccharide (capsule) vaccines, diphtheria vaccine
(kind of COVID vaccine)
