Flashcards in Immune Pathology I: Immunopathology of Hypersensitivity Reactions Deck (42):
Sever systemic Type I hypersensitivity response
-acute respiratory distress (bronchiole constriction with air trapping, laryngeal obstruction, pulmonary edema)
Type II hypersensitivity is mediated by _______.
Treatment for Anaphylaxis
Rapid delivery of epinephrine (EpiPen)
- decreases vasodilation, relaxes bronchial smooth muscle
Mechanisms of injury (Type II Hypersensitivity)
- tissue damage through activation of complement cascade and PHAGOCYTOSIS by immune cells
-->autoimmune hemolytic anemia
- tissue damage through activation of complement cascade and INJURY from inflammatory cells (release of inflammatory mediators)
--> Goodpasture syndrome
- Direct CELL KILLING by cytotoxic cells (NK cells)?
- Antibody binding to cell impairs normal function
--> myasthenia gravis and Graves' disease
What are transfusion reactions (Type II Hypersensitivity)?
- Antibodies form against and bind to antigens on incompatible blood
- leads to lysis of RBCs (hemolysis)
What is Goodpasture's Syndrome? (Anti-GBM disease)
Antibodies produced against components of basement membranes
-->target KIDNEY (glomerular basement membranes) and LUNG (alveolar basement membranes)
What is autoimmune hemolytic anemia? (Type II Hypersensitivity)
- patient forms antibodies against antigens on their own RBCs
- also leads to hemolysis
What are the treatments for Goodpasture's syndrome?
-plasma exchange (remove offending antibodies); take out a lot of good antibodies as well while doing this, renders them more susceptible to infection
What are the effects of Anti-GBM disease?
-acute kidney injury with blood in urine
- acute pulmonary hemorrhage
Type III Hypersensitivity is mediated by ______
What are the steps of Type III Hypersensitivity?
– Antibodies bind to antigen in circulation and form complexes (Ab-Ag)
– Complexes lodge in tissue, activate complement
– Recruitment of inflammatory cells and release of
mediators --> tissue injury
Describe Post-Streptococcal Glomerulonephritis (clinical example of Type III Hypersensitivity)
- Occurs 2-4 weeks after skin or throat infections with certain forms of Streptococcus bacteria
- Acute kidney disease due to glomerular injury
--> Antibodies form against antigens from the strep
-->Ab-Ag immune complexes lodge in glomerulus
-->Acute inflammatory response “glomerulitis”
- Causes glomerular dysfunction
• Complete resolution in most cases
What are two clinical examples of Type III Hypersensitivity?
- Systemic Lupus Erythematosus (autoimmune disease)
- Post-infectious glomerulonephritis
Type IV Hypersensitivity are ____-mediated
Type IV Hypersensitivity are CELL-mediated
What are the steps of Type IV Hypersenstivity?
– First mechanism (delayed type):
• Antigen-presenting cell activates CD4+ T-cells
• CD4+ T-cells activate macrophages, PMN’s tissue
• If antigen persists, may result in formation of granulomas– 2nd mechanism (cytotoxic type):
• Antigen-presenting cell activates CD8+ T-cells
• CD8+ T-cells directly destroy antigen-bearing cells
What are two types of clinical examples for delayed type, type IV hypersensitivity?
Granulomatous inflammatory diseases:
What are the two mechanisms of Type IV Hypersenstivity?
-First mechanism (Delayed type)
-Second Mechanism (cytotoxic type)
What are two types of clinical examples for cytotoxic type, type IV hypersensitivity?
- killing of virally infected cells
- T-cell mediated rejection of transplanted organ
Describe contact dermatitis and give its gross and microscopic presentaiton
-Skin reaction which developes following exposure to specific antigen
-->latex, poison ivy, poison oak, nicke
-erythema (redness of skin) 4-6 hours after exposure
What is immunopathology?
- the process by which the host's cells/tissues are injured through the host's immunologic reaction to a stimulus
- may be incidental to an appropriate immune response (innocent bystander)
- may be specifically directed to the host's cells/proteins/tissues (self response)
What is the sequence of events from when a macrophage takes up an antigen (general sequence)?
Macrophage takes up antigen and presents it to T and B cells:
- B lymph activated and differentiates to plasma cell which produces antibodies
- T lymph activated and releases lymphokines
There are four classes of hypersensitivity reactions, define each type.
- type I: allergic/anaphylactic type
- type II: antibody-dependent type
- type III: immune complex type
- type IV: cell-mediated type
What are the steps in type I hypersensitivity?
- antigen (i.e. pollen) activates a T helper cell to costimulate a B cell to secrete IgE antibodies
- IgE secreted and IgE bind to mast cell receptors
- Mast cells degranulate and release mediators (vasoactive amines, lipid mediators, and cytokines)
In repeat exposure of type I hypersensitivity, what occurs?
- Mast cells are activated and release mediators (vasoactive amines, lipid mediators, and cytokines)
Vasoactive amines and lipid mediators (released by activated mast cells in type 1 hypersensitivity) result in what?
immediate hypersensitivity reaction (minutes after repeat exposure to allergen)
Cytokines (released by activated mast cells in type 1 hypersensitivity) result in what?
late phase reaction (2-24 hrs after repeat exposure to allergen)
see eosinohpils here
What are mediators released by mast cells (type 1)?
- HISTAMINE (involved in vasodilation, increased vascular permeability) - act in minutes after exposure
- neutrophil chemotactic factor (attract neutrophils)
- enzymes (cause tissue injury)
What are the two forms of type 1 hypersensitivity and give examples
-->seasonal allergies/rhinitis, urticaria (hives), asthma, insect bite
- systemic (anaphylaxis)
Asthma (local form of type 1 hypersensitivity) shows what changes in histology of lung tissue?
- thickening of smooth muscle (due to repeated constriction of airways)
- thickening and wrinkling of basement membrane of bronchioles)
- increased mucus production
What steps are involved in type II hypersensitivity (antibody-mediated type)?
- antigen exposure causes antibodies to be released by B cells
- antibodies attach to antigens on cells and cause direct injury to cell
Contrast Type I and Type II hypersensitivity in terms of cells involved
Type I: (ALLERGIC)
- involves B cells (plasma cells) that secrete antibodies; T helper cells that activate B cells; mast cells; antibodies (IgE); eosinophils
Type II: (antibody-mediated)
- host cells; macrophages, NK cells; and the complement system
Contrast Type I and Type II hypersensitivity in terms of diseases resulting from each
- can cause localized immune response, like HAYFEVER or ASTHMA (wrinkles basement membrane in bronchioles, causing constriction); causes muscular hypertrophy in bronchi; excess mucus glands/hyperplasia. causes air trapping in lungs, narrows laryngeal channel.
- can cause whole body response, like ANAPHYLAXIS (can cause death in minutes due to respiratory difficulties)
- TRANSFUSION REACTIONS, where body lyses blood cells because it is a mismatch to self (recognized as antigen). AUTOIMMUNE HEMOLYTIC ANEMIAS - can also be drug-induced, like from a penicillin reaction causing the body to destroy the body's RBCs
- GOODPASTURE DISEASE: body generates antibodies to the basement membrane in the glomeruli and in the alveoli. Causes pulmonary hemorrhage and blood in the urine.
- MYASTHENIA GRAVIS and GRAVES' DISEASE
What are the cell/tissue targets for two examples of Type II hypersensitivity?
- Goodpasture disease targets the CELLS IN THE BASEMENT MEMBRANES in the glomeruli and the alveoli
- hemolytic anemia can be caused by a drug-induced reaction to self RBCs; or in a mismatched transfusion, the body will attack RBCs
What is Type III hypersensitivity (definition)?
Antigen-antibody complexes circulate in the bloodstream and deposit in tissues, leading to localized inflammation and tissue damage
What is Type II hypersensitivity (definition)?
Antibodies directed toward antigens present on cells or other tissue components, causing cell/tissue damage
(when ag-ab complexes activate complement pathway, various complement components are consumed and level of complement in blood will fall - useful in diagnosis)
What is Type I hypersensitivity (definition)?
Rapidly evolving immune reaction occurring within minutes of combination of antigen and antibody bound to previously sensitized cell
What is Type IV hypersensitivity (definition)?
Cell-mediated tissue damage caused by sensitized T-lymphocytes
Contrast Types I and III hypersensitivities
small Ag-Ab complexes float through circulatory system. Due to size, they are less likely to be broken down in liver or spleen. Eventually they get stuck somewhere in circulation. They activate complement, which attracts neutrophils, which can then release proteolytic enzymes. Type III mostly mediated by IgG and some IgM antibodies. The antigens then are more likely to cause these classes of antibodies to be released, and these types of antibodies cannot cause type I hypersenstiivity.
involves antigens and antibodies that are recognized by mast cells. These particular antigens are more likely to produce a response in the form of IgE antibody, which then interacts with mast cells which release histamine. Individuals more prone to Type I hypersensitivity preferentially produce more T helper cells that favor IgE class switching.
Mechanism in each is fairly similar, but different responses due to Ig class.
Outline the immunologic steps in the development of post-Streptococcal glomerulonephritis as an example of type III hypersensitivity.
- post-streptococcal glomerulonephritis occurs after an acute infection with Streptococcus
- as infection occurs, body recognizes pathogen as foreign and will mount an immune response to fight it off. Antibody will form.
- takes about 2-4 weeks for antibody levels to rise enough to cause this problem
- antigen-antibody complexes (with pathogen) can become lodged in glomerulus
- blood can't flow through the glomerulus; pressure builds, and the glomerulus can become damaged
- causes glomerular injury; acute renal disease
- usually completely resolves
What are three other diseases (other than post-Streptococcal glomerulonephritis) mediated by Type III hypersensitivity?
- serum thickness (rare now), due to treatment with serum from animal source. this would provide antibodies but also proteins from the animal that the body recognizes as antigenic. 10-14 days later blood would develop in urine due to glomerular damage
- systemic lupus erythematosus
Contrast the elements of Type III (immune complex type) from those of Type IV (cell-mediated) delayed hypersenstivity
Type IV delayed
- activated CD4 T cells release cytokines that either
--> activate macrophages
--> call in neutrophils that will cause tissue injury
- activated CD8 T cells directly lyse cells
- the reaction is delayed (due to pathway of B and T cells)
- Ag-Ab complexes free float through circulation and get stuck in areas where they impair the function, like in the glomeruli. This raises pressure and causes glomerular damage.
Type IV uses CD4 and CD8 cells to activate cell lysis or other WBCs.
Type III uses Ag-Ab complexes, of which the antibodies were secreted by B cells