Lecture 17 Flashcards
Allergy/hypersensitivity
An exaggerated misdirected immune response that damages self tissue
Autoimmunity
Abnormal responses to self-antigen
Immunodeficiency
Immune function is incompletely developed, suppressed, or destroyed
Type I hypersensitivity
All have similar mechanism, fast /acute onset
IgE and mast cells
Localized or systemic
Type I hypersensitivity mechanism
Allergens enterand and are picked up by dendritic cell, dendritic presents to T helper cell on MHC II in lymph node, T helper activates B cell, B cell divides and produces plasma cells that make IgE specific to the allergen, Fc fragments on IgEs bind mast cells creating primed mast cells
When allergen encountered again it binds directly to primed mast cells causing degranulation leading to watery eyes, runny nose, etc
Sensitizing dose
Upon first exposure to the allergen IgE for the allergen is made and binds mast cells
Provocative dose
Subsequent exposure to the allergen where sensitized mast cells release chemical mediators that trigger allergy symptoms
Chemical mediators from mast cells
Histamine constricts bronchioles leading to wheezing, coughing, trouble breathing
Histamine binds smooth muscle of vessels and causes them to relax leading to vasodilation
Leukotriene asthma bronchiole constriction
Atopic allergy
Type I, local, chronic includes asthma and hay fever
Hay fever
Marked by seasonal acute inflammation of eyes (conjunctiva) and mucous membranes of the respiratory passage
Sneezing coughing
Asthma
Respiratory disease marked by extreme sensitivity to allergens
Eczema
An acute or chronic allergy of the skin causing itching and burning sensation
Food or drug allergies
Considered localized or atopic
Allergies are classified by
How they enter the body
Inhalants, ingestants, contactants, injectants
Systemic anaphylaxis
Most severe level of a type I hypersensitivity where mast calls all over the body are sensitized releasing tons of histamine leading to bronchiole constriction and vasodilation
Shock: major drop in blood pressure
Suffocation
Most common causes of systemic anaphylaxis
Food, insect stings, antibiotics, and latex
Corticosteroids
Inhibit B and T cells, can be given to help bad allergies but weaken immune system
Antihistamines
Popular treatment and active ingredient in most over the counter allergy drugs work by blocking histamine receptors on target organs
Compete with histamine
Cromolyn
Prevents degranulation of mast cells
Epinephrine
Counteracts effects of histamine, should be carried by people susceptible to anaphylaxis
Type II hypersensitivity
Involve complement assisted lysis of foreign cells by IgG and IgM antibodies against the cell’s foreign surface antigens
Includes transfusion reactions
Type II hypersensitivity
When the wrong blood type is transfused IgG and IgM antibodies clump donated blood into an agglutination complex which can block circulation, activates complement causing membrane attack complex leading to hemolysis of donated blood cells and anemia
3 months
Preformed antibodies against foreign blood type antigens
Rh factor
Glycoprotein surface antigen, dominant trait, 85% humans, no preformed antibodies against Rh factor, sensitized by Rh negative individual getting exposed to RH factor
Routes of exposure for RH factor
Transfusion or placental sensitization
Hemolytic disease of newborns
During labor some RH+ from baby can get into mom’s circulatory system activate immune system and create memory IgG against RH making mom sensitized, then for next child if RH+ IgG antibodies against RH cross antibodies and bind fetal blood cells activating complement causing lysis of fetal blood cells
Leads to miscarriage or if less antibodies are made and cross placenta may have mild effects from distress later in life
RhoGAM
Anti-RH antibodies given to RH- moms before and after labor that neutralize any baby blood that leave into mom’s system before her immune system reacts and becomes sensitized
Type III hypersensitivity
Soluble antigen reacts with antibodies IgG and IgM which form immune complexes that deposit in the tissues and trigger complement resulting in inflammatory responses and damage to the tissues
Type III mechanism
Antibody combines excess soluble antigen forming large complexes, the complexes become lodged in basement membranes of the epithelia of vessels kidney skin and other sites, complement factors trigger release of histamine and mediators, neutrophils migrate to immune complex sites and release enzymes and chemokines that severely damage tissues
Arthus reaction
Acute response to a second injection or vaccines at the same site as first injection
Causes area to become red, hot, swollen, painful
Usually cleared on its own
Severe cases intravascular blood clotting
Serum sickness
Immune complexes formed from exposure to animal serum (proteins)
Leads to kidney, heart, skin, and joint damage
Type IV hypersensitivity
Delayed response to antigens that involves t-cell mediated immunity
T cells respond to antigens on self tissue or transplanted foreign cells
Graft rejection where cytotoxic T cells recognize foreign MHC
Contact dermatitis
Type IV hypersensitivity, requires 2 exposures, liquid soluble chemicals are absorbed by skin, picked up by dendritic cells close to the epithelium pick up allergen, process it, and display on MHC, previously sensitized T helper cells that recognize and activate secreting cytokines to attract macrophages and cytotoxic T cells, macrophages secrete mediators causing local inflammation then cytotoxic T cells directly kill skin cells
Autograft
Tissue from one site of body to another site of their body no rejection risk
Isograft
Tissue from an identical thin, minimal rejection risk
Allograft
Most common type involving exchanges between genetically different individuals belonging to the same species
Varying rejection risk based on MHC similarity
Xenograft
Transplant exchange between individuals of different species
Graft versus host disease
Especially in bone marrow transplants, the graft cells attack host
Graft tissue has own cytotoxic T cells that don’t recognize the recipient’s MHC
Autoimmunity
Developing hypersensitivity to your own cells in which antibodies and/or autoreactive T cells attack self antigens
Autoimmunity causes
1) lost ability to determine self vs non-self from colonal deletion failing or improper selection of T cells
2) mutations to TCR and BCR
3) appropriate antigen is similar to self tissue
4) viral infection triggers attack
Autoimmune more common in females
Systemic lupus erythematosus
Produce antibodies to DNA and cellular material damages multiple organs and has distinctive butterfly rash
Treat steroids to weaken immune system
Rheumatoid arthritis
systemic autoimmune, Produce antibodies against joint tissue, chronic inflammation leads to scar tissue and joint damage
Type I diabetes
Produce antibodies to insulin-secreting islet cells (beta cells) of the pancreas can also develop autoreactive T cells can develop and actively destroy islet cells
Reduces insulin production
Insulin essential to cellular uptake of glucose
Multiple sclerosis
Produce antibodies against myelin sheath around nerves, autoreactive T cells can also contribute to destruction of nerves
Diminished capacity of neurons to send impulses leading to neuromuscular disease
Muscle weakness, tremors, speech, vision problems, paralysis
Myasthenia Gravis
Produce antibodies against acetylcholine receptors on muscles, no muscle contraction from blocked receptors, results in muscle paralysis
Immunodeficiency diseases
Components of the immune response system are absent involving B and T cells, phagocytes, and complement
Recurrent overwhelming infections with opportunistic pathogens
Primary immunodeficiency
Genetically-based rack of immunity that is present at birth
Secondary immunodeficiency
Acquired after birth and caused by natural or artificial agents like infections, cancer, drugs, or radiation
Di Georgesyndrome
Most severe immunodeficiency underdeveloped or no thymus, can’t create T cell receptors in thymus, no cell-mediated immunity
Recurrent infections
agammaglobulinemia
Make no antibodies, caused by B cells that don’t make plasma cells, affects humoral immunity
Severe combined immunodeficiencies (SCIDs)
Most dire and lethal of immunodeficiencies, lack stem cells that develop into B and T lymphocytes, no immune system
Bone marrow transplant containing B and T cans
No rejection
Cancer
Growth of abnormal cells, repeated and uncontrolled cell division forming tumor
Benign tumor
Self-contained mass that doesn’t invade or impede other tissues
Malignant tumor
Uncontrolled growth that does impact tissue function and spreads to other sites
Cancer causes
Mutations in tumor suppressor genes that play a role in telling cell to stop dividing or correcting
Viral infections can carry oncogenes that cause cell to divide uncontrollably
Environmental factors
Immune system + cancer
Cell mediated immune system does surveillance and cells with cancerous proteins are destroyed
Cytotoxic T cells release perforins and granzymes
Dramatic cancer risk increase
Immunocompromised patients that lack adequate surveillance (T cells)
