Immunology Flashcards
(31 cards)
Type 1 hypersensitivity reaction mechanism
Initial sensitization to the antigen (allergen)
- helper T cells and B lymphocytes are activated by the same antigen ( allergen ), e.g. food; pollen; mold; drug
- helper T cells cause B cells to make IgE antibody
- IgE antibody sticks to the surface of mast cells which contain granules with histamine
Type 1 Hypersensitivity reaction
typical called immediate time because onset is seconds to minute
immediate allergic response to an antigen ( allergen ) to which an individual was PRECIOUSLY SENSITIZED
Localized (involving upper and lower respiratory tract, or GR tract)
or Systemic and life threatening ( anaphylactic reaction)
Allergic Response tends to occur in genetically susceptible individuals.
Type 1 Hypersensitivity Reaction
Second exposure to antigen
- allergen binds adjacent IgE antibodies on mast cells causing cross linkage of IgE and mast cell IgE receptors
- mast cell IgE receptors are activated and initiate a sequence of cell signaling reactions in mast cells
- mast cell granules fuse with the cell membrane and release histamine (within seconds)
Effects of histamine
a. dilate blood vessels; make blood vessels leaky
( tissue becomes locally red and swollen; blood pressure may decrease systemically )
b. constrict smooth muscle (e.g. within bronchi causing narrowing of bronchi and difficulty with breathing; within GI tract causing diarrhea and/or vomiting)
c. depolarize nerves causing itching
d. constrict smooth muscle (e.g. within bronchi causing narrowing of bronchi; within GI tract causing diarrhea and/or vomiting)
Urticaria (Hives)
- symptoms: discrete itchy (pruritic), red, swollen lesions
2. examples of allergens: food; drugs
ALLERGIC RHINITIS (when seasonal, is called “hayfever”)
- symptoms: clear nasal discharge (rhinorrhea); itching of nose; sneezing; symptoms of tearing and itching of eyes may be present
- allergens ( examples)
tree pollens; grasses; molds; household dust mites (small arthropods); animal dander (hair or feathers from animals)
Anaphylactic Reaction
A. symptoms:
- severe lowering of blood pressure (shock) due to widespread dilation of blood vessels
- severe respiratory compromise due to constriction of airways (bronchospasm) and swelling of larynx
- localized area of swelling: e.g. swelling of eyelids due to bee sting on face
- generalized hives may develop on the body
B. common triggering allergens: drugs ( e.g. penicillin); insect venom ( e.g. from bee sting); latex (typically in gloves used in medical practice); foods (e.g. peanuts; shellfish)
Note: latex allergy to be discussed with type IV hypersensitivity reaction
TYPE II HYPERSENSITIVY REACTIONS
I. IMMUNE MECHANISM
ANTIBODIES (IgG or IgM) CAUSE DESTRUCTION OF BODY TISSUE CELLS BY a few mechanisms; important mechanisms are:
A. Antibody binds to an antigen on a cell and activates complement proteins; the complement membrane attack complex (MAC) forms on tissue cell and “drills holes” in cell; this causes tissue cell to come apart
B. Antibody binds to an antigen on a cell and promotes phagocytosis of cell (often by macrophage)
EXAMPLE OF TYPE II HYPERSENSITIVY REACTIONS
RED BLOOD CELL TRANSFUSION REACTION:
A. patient given red blood cells into a vein (transfused) for example, if he has had severe blood loss due to trauma
B. patient and donor red blood cell antigens are incompatible; patient has an antibody that binds to a foreign antigen on the donor’s red blood cells→complement is activated on the surface of the donor red blood cells→complement membrane attack complex
of proteins forms on surface of donor red blood cells
C. membrane attack complex “drills” a multitude of “holes” into donor red blood cells→donor red blood cells fall apart
D. other complement proteins that form may cause life threatening problems such as severe drop in blood pressure in the patient
TYPE III HYPERSENSITIVITY REACTION
CIRCULATING ANTIGEN-ANTIBODY COMPLEXES (antibody is IgG or IgM) GET DEPOSITED IN TISSUES SUCH AS THE KIDNEY; BLOOD VESSELS, OR JOINTS→
Complement is activated, and complement proteins lead to local tissue destruction by attracting neutrophils to the site→
neutrophils release chemicals (e.g. enzymes) which destroy the surrounding tissue
EXAMPLE OF TYPE III HYPERSENSITIVITY REACTION
POST-STREPTOCOCCAL GLOMERULONEPHRITIS
MECHANISM
A. a young child has a sore throat (pharyngitis) caused by certain strains of group A Streptococcus
B. an antibody is made to a Streptococcal antigen and binds to the Streptococcal antigen in the circulation forming an antibody-antigen complex (there is a large amount of this antigen in the blood)
C. the antibody-antigen complex travels in the blood to the kidney, where the complex gets deposited (in the glomerulus)
D. the antigen-antibody complex in the kidney activates complement, and certain complement proteins cause neutrophils to accumulate in the kidney
E. the neutrophils release enzymes which destroy kidney tissue (in the glomerulus)
F. the child presents with evidence of kidney injury 1-3 weeks after
the episode of sore throat:
high blood pressure; blood in the urine; swelling around the eyes; abnormal lab tests of kidney function
(this type of kidney disease will be discussed in nephrology section of clinical pathophysiiology course)
Differences between type II and type III hypersensitivity reactions:
Type II: focused “assassination of a cell” due to binding of antibody to a specific antigen on surface of the target cell →
- leads to complement activation→membrane attack complex forms on cell and destroys cell
- leads to phagocytosis of cell (often by macrophage)
Type III: unfocused killing of a “crowd of cells- innocent bystanders”
Antibody-antigen immune complex traveling in blood deposits in a location (e.g. kidney) and activates complement→ attracts neutrophils to site; neutrophils release destructive enzymes into the “crowd of surrounding cells” and kills them
TYPE IV HYPERSENSITIVITY REACTION
MEDIATED BY T CELLS: ANTIBODIES ARE NOT INVOLVED
Traditionally called “delayed type” hypersensitivity reaction because onset is typically within 2-3 days
I. IMMUNE MECHANISM
A. prior sensitization to an antigen is required:
an antigen is presented to helper T cells and cytotoxic T cells by an antigen presenting cell (e.g. macrophage), which activates the T cells, and causes them to make many more of themselves (memory T cells are made)
(this process takes at least 1 week)
B. re-exposure to the same antigen results in tissue injury by different mechanisms
Activation of memory T cells and accumulation of them at the site with subsequent tissue injury typically takes 1- 3 days
- activated memory helper T cells do the following:
a. release cytokine ( chemical messenger ) which activates macrophages
b. macrophages mediate alterations in blood vessels and tissue damage - activated memory cytotoxic T cells directly destroy tissue cells (e.g. by perforating their membranes )
EXAMPLE OF TYPE IV HYPERSENSITIVITY REACTION
AND MECHANISM
- most common example of type IV hypersensitivity reaction
- common in the general population, and most frequent occupational skin diseaseDEFINITION:
an area on the skin which had been in contact with certain types of chemicals becomes red, swollen and itchy; area may develop blisters and later “weeping” and crustingMECHANISM. - prior sensitization occurs: (the sensitization or afferent phase)
a. a low molecular weight chemical ( often ionized nickel or oil from poison ivy) penetrates into the skin and binds to a protein in the skin→ this stimulates an abnormal immune response:
an antigen presenting cell (antigen presenting cells in the skin are called dendritic cells) responds to the protein- chemical complex as foreign and takes it inside the cell (where it gets “chopped up” so it can be presented as an antigen to T cells)
b. The dendritic cell travels to a nearby draining lymph node and presents the antigen to helper T cells and cytotoxic T cells.
c. the helper and cytotoxic T cells are activated, proliferate and make memory cells. (Memory cells will respond much quicker when exposed to the same antigen again)
d. the memory T cells exit lymph node and circulate throughout the body
e. this initial sensitization phase takes at least 1 week
note: strong sensitizer (poison ivy):
sensitization occurs in 7-10 days
weak sensitizer: sensitization occurs after months-years
- efferent phase: skin rash typically develops after 1-3 days upon re-exposure to the chemical
a. It takes this amount of time for the memory helper and cytotoxic T cells to be recruited to the site of chemical contact in the skin, become activated, and mediate damage to the skin.
b. Helper T cells stimulate macrophages, which in turn cause release of inflammatory mediators (e.g. histamine) that bring about a skin rash associated with redness, swelling and itchiness
c. Cytotoxic T cells can directly create damage in the skin resulting in blister formation
IRRITANTS THAT MAY CAUSE ALLERGIC CONTACT DERMATITIS
- some of the more common causes of allergic contact dermatitis:
a. poison ivy, oak or sumac: most common cause of allergic contact dermatitis in North Americab. nickel: found in many objects which have contact with skin e.g. jewelry, belt buckles, watches, buttons
c. antimicrobial agents applied to the skin: bacitracin; neomycin
d. hair care products (e.g. dark hair dyes); creams; cosmetics; soaps
e. latex (gloves in medical setting are a common source)
AUTOIMMUNITY
A. diseases associated with tissue injury that is caused by inappropriate activation of the immune system upon exposure to self antigens in genetically susceptible persons
B. Tissue injury may result from a variety of mechanisms
Example:
antibodies may be made which bind self antigens
(called “autoantibodies”) →
autoantibody binds an antigen on a tissue cell and activates complement→
membrane attack complex (MAC) forms on patient’s tissue cell→ patient’s tissue cell is destroyed by MAC
SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)
A. DEFINITION
1. prototype of multisystem autoimmune diseases
2. patients develop disease involving multiple organs due to a a variety of well characterized autoantibodies→ autoantibodies result in tissue destruction in many organs:
organs involved: skin; joints; kidneys; brain; blood vessels; membranes covering lungs and heart
B. INCIDENCE OF SLE: female to male ratio = 9:1 ( significant female predominance )
C. CLASSIC PRESENTATION OF SLE
- young female with “butterfly rash” on her face
- fever
- pain and swelling of joints
- chest pain due to inflammation of pleura (membranes covering lungs and thoracic cavity)
CLINICAL FEATURES SUSPICIOUS FOR PRIMARY IMMUNODEFICIENCY
hereditary immunodeficiency disorders typically present in infants 6 months-2 years ( after the mother’s protective antibodies have disappeared)
a. chronic or recurrent infections which do not respond to appropriate antibiotic therapy and/or are caused by unusual microbial agents
b. growth failure/failure to thrive
c. patients have life threatening infections
d. patients have multiple sites of infection
e. recurrent diarrhea
Isolated IgA deficiency
most common inherited immunodeficiency disease (incidence: 1/700 Caucasians- disease has varied severity)
- deficient immune component: level of IgA antibody may be severely decreased (
EXAMPLE OF A CASE OF IgA DEFICIENCY
B CELL
29 year old female diagnosed with IgA deficiency after the following history: multiple episodes of pneumonia as a toddler; repeated episodes of diarrhea in childhood, 1 requiring hospitalization; repeated episodes of throat infection (pharyngitis) in her twenties;
life threatening toxic shock syndrome developed 5 days after delivery of her 1st child
- IgA deficiency in this patient caused the various infections involving the upper and lower respiratory tract (pneumonia and throat infections), gastrointestinal tract (diarrhea) and genital tract (toxic shock syndrome after delivering baby)
- these diseases occur because IgA normally protects the surfaces of these tracts from microbial invaders ( a lot of IgA is normally present in the mucosal secretions in the lumens of these body tracts )
x-linked agammaglobulinemia (Bruton disease)
B cell
1 of more common primary immunodeficiency diseases
the word “agammaglobulinemia means without immunoglobulins
( immunoglobulins are antibodies)
- deficient immune components: LACK of ALL CLASSES of immunoglobulins ( because B cells do not mature)
- patients have significant recurrent bacterial infections
T CELL IMMUNODEFICIENCY DISEASE
DiGeorge Syndrome
partial or complete lack of thymus development
1. deficient immune components: T cells
( thymus is needed for maturation of T cells)
- infants extremely vulnerable to microbial infections in which T cells play an important role in host defense: viral; fungal; protozoan infection; infections caused by intracellular bacteria
IMMUNODEFICIENCY ACQUIRED FROM DRUG TREATMENT WHICH SUPPRESSES THE IMMUNE SYSTEM
drugs given to patients with autoimmune diseases to prevent the patient’s immune system from destroying their tissues (such as prednisone)
IMMUNODEFICIENCY ASSOCIATED WITH SYSTEMIC DISEASE
ACQUIRED IMMUNODEFICIENCY SYNDROME (AIDS)
more than 22 million people have died worldwide from AIDS since the epidemic was recognized in 1981
1. caused by infection of helper T cells by human immunodeficiency virus (HIV): results in severe depletion of helper T cells
2. helper T cells are the “generals of the immune system”:
they direct the actions of B cells, cytotoxic T cells and macrophages in protecting the body from microbial organisms and tumor cells
3. without helper T cells, patients are vulnerable to many infections and cancers that persons with normally functioning immune systems do not get
