Flashcards in Immune Hypersensitivities (Buxton) Deck (84):
Define immune hypersensitivity.
Tissue damage due to immune mechanisms.
This type of immune hypersensitivity involves "allergic" or atopic reactions in which you'll encounter IgE, mast cells, and eosinophils.
This type of immune hypersensitivity is due to antibody binding to cell surface proteins.
This type of immune hypersensitivity involves immune complex deposition in tissues, followed by complement activation and acute inflammation.
This type of immune hypersensitivity involves excessive tissue damage instigated by CD4 T cells and mediated by activated macrophages and cytotoxic T cells.
What are the 3 phases of Type I immune sensitivity?
Sensitization, immediate reaction, late-phase response
During this phase of Type I immune sensitivity there is an initial exposure to the allergen, to which the body responds by making IgE. IgE leaves the plasma cell and goes through the blood to the various tissues containing mast cells. IgE then inserts itself into the Fc receptor on the mast cell, eventually building up over time.
During this phase of Type I immune sensitivity the allergen crosslinks 2 or more IgE molecules on the mast cell membrane after a sufficient amount of IgE to that allergen has been produced.
What is the consequence of crosslinking?
Degranulation, eiconasoid production, and synthesis and release of cytokines.
During this phase of Type I immune sensitivity, which occurs 6-24 hours after mast cell degranulation, tissue damage due to infiltration of eosinophils (and some neutrophils and mononuclear cells) into affected tissue becomes apparent.
Late phase response
Name 6 players in the atopic reaction.
Name 5 clinical syndromes associated with Type I hypersensitivity.
Sinusitis (hay fever)
Anaphylaxis (systemic response)
Where can you find mast cells?
Skin and mucous membranes
What are the contents released during degranulation?
Chemotactic factors (ECF, NCF)
What is the characteristic infiltrate of allergic/atopic reactions?
What leads to the mast cells activation? What does this activation lead to?
Binding of antigen to IgE-coated Fc receptors on the mast cell. This leads to degranulation (immune response).
What does granule exocytosis via granule with preformed mediators result in?
Vascular dilation, smooth muscle contraction, tissue damage. This takes place within minutes.
What does secretion via lipid mediators result in?
Vascular dilation, smooth muscle contraction, chemotaxis. This takes place within hours.
What does secretion via cytokines result in?
Inflammation (leukocyte recruitment). This takes place within hours.
What is the purpose of skin testing?
To identify specific allergens to which a patient reacts.
What are the steps of skin testing?
1. Inject/introduce small amount of allergen into skin.
2. Allergen binds to anti-allergen specific IgE on skin mast cells.
3. Mast cells degranulate - see flair and wheal with positive response.
When mast cells degranulate, they release ______, which induces ______ and increases ______ _______, resulting in flair and wheal.
What is flair?
What is wheal?
How long does it take for the skin testing reaction to occur? How long does it last?
5-15 minutes; less than 30 minutes
What are the consequences of Type II immune hypersensitivity?
Complement-mediated cell or tissue damage
Altered signaling if antigen is a cell-surface receptor
Which Ig are involved with Type II immune hypersensitivity?
IgG & IgM
What are some diseases mediated by Type II immune hypersensitivity?
Autoimmune hemolytic anemia, autoimmune thrombocytopenic purpura, Pemphigus vulgaris, Goodpasture's syndrome, Acute rheumatic fever, Myasthenia graves, Graves' disease (hyperthyroidism), Pernicious anemia
Hemolytic anemia utilizes which consequence of Type II immune hypersensitivity?
Autoantibody to RBC cell surface antigens binds, complement is activated, and cells are coated with C3b. As these cells pass through the spleen, they are phagocytized by splenic macrophages, leading to anemia. This is an example of Type II hypersensitivity.
If no avenues of treatment work for hemolytic anemia, what can you do?
Remove the spleen.
Rh(+) = has antigens on RBC
Rh(+) father & Rh(-) mother are pregnant with 1st child. Rh antigens from developing fetus can enter mother's blood during delivery, to which she will respond by producing anti-Rh antibodies. During her next pregnancy with another Rh(+) fetus, her antibodies will cross the placenta and damage fetal red blood cells. This is an example of Type II hypersensitivity.
Hemolytic anemia of the newborn
Autoantibody to desmosomes (responsible for keeping skin together; like glue) to which the cell responds by contracting its cytoskeleton, causing the cells to pull apart. This is an example of Type II sensitivity.
What is the clinical presentation of Pemphigus vulgaris?
Large blisters form in the skin and mucous membranes
Autoimmune disease in which the body makes antibodies to perceived antigens in the collagen (type IV) of the basement membrane in glomeruli and lungs. This is an example of Type II sensitivity.
What is the target antigen in anti-glomeruli basement membrane disease?
An epitope in the globular, non-collagenous domain (NC1) of the alpha 3 collagen chain in type IV collagen.
Which part of the complement system is better at attracting neutrophils?
How does complement-mediated cell damage occur in anti-glomeruli basement membrane disease?
C5a binds by complement receptor or Fc receptor. It then "throws up" - "frustrated phagocytosis"; since it can't do its job of phagocytizing due to the large size of the antigen, C5a degranulates.
What are clinical symptoms of complement-mediated cell damage in anti-glomeruli basement membrane disease?
Blood in urine, coughed-up blood - this is highly fatal
Antibody-mediated cellular dysfunction in which the antibody stimulates a receptor without the associated hormone - in this case, antibody is directed against thyroid-stimulating hormone receptor.This is an example of Type II sensitivity.
What is the clinical consequence of Graves disease?
Antibody-mediated cellular dysfunction in which the antibody stimulates a receptor without the associated hormone - in this case, antibody is directed toward acetyl-choline receptor, blocking it so that acetyl choline cannot degranulate and stimulate muscle contraction. This is an example of Type II hypersensitivity.
What is the clinical consequence of Myasthenia Gravis?
Profound muscle weakness
What is the characteristic infiltrate of Type III hypersensitivity?
What is the immune complex composed of?
Several IgG molecules and antigens, which may be autologous or microbial in origin.
Where do immune complexes tend to deposit?
Glomeruli, joints, artery walls, skin
What happens to small immune complexes?
They can pass through the kidney and be secreted.
What happens to large immune complexes?
They can be disposed of via macrophages.
What happens to medium immune complexes?
They may precipitate out of solution into tissues, especially those with high capillary density, leading to complement activation.
Which parts of the complement system lead to degranulation of histamine from mast cells?
C3a & C5a
What type of cells are effected the greatest by eicosanoids and substances in granules?
What condition involving Type III hypersensitivity might you expect to encounter following Streptococcus pyogenes skin or pharyngeal infections?
What condition involving Type III hypersensitivity might you expect to encounter in patients with falciparum malaria or bacterial endocarditis?
What condition involving Type III hypersensitivity might you expect to see in patients with joint pain due to HPV B-19, rubella virus, or HBV infections?
What condition involving Type III hypersensitivity might you expect to see in patients with HBV?
What symptom might a Type III hypersensitivity cause in patients with HPV B-19 or rubella virus infections?
When an auto-antigen is involved, what kind of disease are are we talking about?
What are the 3 types of antigens responsible for Type III hypersensitivity?
Infectious microbial antigen
Certain cancers that can release sufficient antigens to develop a Type III hypersensitivity
What type of antibodies will you find in a Type III hypersensitivity?
What type of antibodies will you find in a Type IV hypersensitivity?
What is the characteristic infiltrate of Type IV hypersensitivity?
Why/when does a Type IV hypersensitivity reaction occur?
In response to a particular stimulus of either autologous, microbial, or hapten origin.
What type of inflammation does an infiltration of mononuclear cells signal?
What kind of tissue damage caused by Type IV hypersensitivity is permanent? Why?
Fibrosis tissue damage causes scars from fibroblast activity. Tissue is reorganized.
What are some diseases that an autologous antigen can cause due to a Type IV hypersensitivity?
Rheumatoid arthritis, sarcoidosis, other autoimmune diseases
What are some infectious antigens that can cause a Type IV hypersensitivity?
TB, Histoplasma, viral hepititis
What are some haptens that can cause Type IV hypersensitivity? What mechanism do they use?
Contact sensitivity - poison ivy, nickel, other metals
What would you expect to see with allergic contact dermatitis caused by a Type IV hypersensitivity?
Itchy, erythematous papular rash at site of contact with certain substances. Histologic appearance would include edema and mononuclear infiltrate.
When would you expect to see a rash in someone with a poison ivy allergy? Why?
After the first encounter due to memory cells.
Langerhans cells process and present hapten epitopes. T cells (CD4 & CD8) infiltrate into skin and secrete cytokines. Keratinocytes secrete cytokines in response to T cell cytokines. Cytokine activation promotes inflammation, edema, and stimulation of nerve endings (itchy feeling). Which type of hypersensitivity is this?
Which diseases involve granular formation?
TB, Histoplasma infection, Sarcoidosis
Where do TB and Histoplasma infections reside in the body, and what happens when they get there?
Alveolar macrophages - the macrophages aren't able to kill these things, so to prevent spread, mononuclear cells wall up and form granulomas around them.
How is the granuloma maintained?
Th1 cells orchestrate its constant rebuilding every day.
How might the organism inside the granuloma overcome this barrier?
If the immune system is suppressed and T cells are affected, the wall will fall apart and the organism will start to replicate.
Which T cell mediates granuloma formation?
What cytokines are involved with granulomas?
Cytokines that activate other cells, e.g. IFN-gamma
Chemokines that attract mononuclear cells, e.g. RANTES, MIP, MCP
Cytokines that increase vascular permeability, e.g. TNF, IL-1
What is the purpose of the TB skin test?
To diagnose latent TB infection, although active infection may be detected as well.
Why do you wait 72 hours after injecting a small amount of TB antigen intradermally?
This is how long it takes to get a positive response.
Which hypersensitivity type has a delayed response time? Which has a short response time?
Type IV; type I
What is proof of a positive TB test?
Hard bump containing cells that have arrived due to cytokine response.
What happens with viral hepititis?
CTL infiltrate the liver, killing more hepatocytes than the actual virus does.
What are the 2 appearances of Type IV hypersensitivity?
Strong inflammatory response involving mononuclear cell aggregation
Rheumatoid arthritis is characterized by which hypersensitivity types?
Type III & Type IV
Type III - RF plus IgG IC deposit in joint space (synovial fluid)
Type IV - mononuclear cell infiltration in synovial membrane that leads to reorganization of joint tissue and resorption of bone