Alterations in Immune Response Flashcards
What are the four types of Hypersensitivity rxns?
IgE-Mediated Immediate
IgE Mediated Cytotoxic
Immune complex mediated
Cell-mediated
What are the two phases of Type 1 Immediate Hypersensitivity? What characterizes this phase?
Sensitization of mast cells and Degranulation of mast cell
Anaphylaxis
What occurs during the sensitization of mast cell hypersensitivity Type 1 phase?
antigen leading to IgE antibodies attaching to the mast cells; on next exposure, the antigen now binds to IgE AB
(IL-4 from CD4 cell stimulates B cell, which becomes plasma cell that secretes IgE = IgE binds to mast cell)
What occurs during the degranulation of the mast hypersensitivity type 1 phase? What are the two phases?
Initial response mediators- mast cells degranulate and preformed mediators like histamine are released; leads to vasodilation, inc permeability, smooth muscle contraction, and bronchial constriction
Late response- 2-8 hours later; same effects but last several days (prostaglandins, leukotrienes, cytokines)
NSAIDs block prostaglandin metabolism
What two cells are most important in Type 1 hypersensitivity rxns?
Type 2 helper T cells and mast cells
What is primary and secondary treatment for a Type 1 hypersensitivity rxn?
Primary: Epinephrine (beta 2 is bronchodilator and Alpha 1 is vasoconstrictor), stabilize airway, vascular access
Secondary: zantac, Benadryl, solumedrol
Discharge= prescribe epipen
What two ABs mediate Type 2 Hypersensitivity rxns? what happens during this type of hypersensitivity?
What are the three types
IgM or IgG
ABs are formed against target antigens on surface of self cell or tissue
1). Complement and AB mediated cell destruction
2). Complement and AB mediated inflammation
3). AB mediated Cellular dysfunction
Define complement and AB mediated cell destruction (type 2 hypersensitivity). What is example
deletion of cells targets by AB; can occur by complement system or ADCC
ex: mismatched blood transfusion; hemolytic disease of newborn
Define complement and AB mediated inflammation (type 2 HS rxn). Give example
AB deposited in cell matrix, complement is activated, injury occurs from inflammation
ex: vascular rejection of organ grafts
Define AB mediated cellular dysfunction (type 2 HS rxn) and give example
AB binds to specific target cell receptor which changes cell function
ex: Grave’s disease (activates thyroid cell and increases hormone production)
What is type 3 HS rxn?
Mediated by AB-antigen complex, complement fixation, and localized inflammation
unphagocytosed complexes settle into tissues and excessively activate complement (activates neutrophils and ends in chronic inflammation)
What’s the difference between Systemic and local immune complex disorders for type 3 HS rxns?
Systemic: serum sickness (IgM, IgG, sometimes IgA)
Local: arthus rxn (local inflammation and tissue necrosis from vasculitis)
What is Type 4 cell mediated hypersensitivity?
Cell MEDIATED not AB
Mechanism of response to variety of microorganisms; can lead to cell death and injury in response to chemicals
What is direct cell mediated cytotoxicity under Type $ HS rxn?
CD8 cytotoxic T lymphocytes destroy APCs
What does the delayed type hypersensitivity disorder under Type 4 HS rxn occur under?
how long does it take? give examples
occurs in response to antigens and APCs (macrophages/CD4 helper T ONE cells)
T one helper cells release cytokines- activates macrophages or CD8
takes about 48-72 hrs before T helper system forms effector cell to target antigen
TB test- recognized by T memory cells and rxn occurs
Allergic contact dermatitis- poison ivy takes 12-24 hrs after exposure for rxn
Hypersensitivity pneumonitis: activation of lung cytotoxic t cells in response to inhaled dust (farmer’s lung from chronic exposure)
Graft rejection
Autoimmune disorders
What is self tolerance?
the ability to tolerate your own antigens
Human leukocyte antigens coded by MHC genes serve as recognition markers of self (on most nucleated cells)
What body part deletes problematic T cells? How about B cells?
Thymus
Bone marrow
spleen or lymph nodes (peripheral mechanisms in place for problematic T cells that get missed)
Why do we get autoimmune diseases?
No definite reason
- know in women, estrogen stimulates the immune system
- could be inheritance of susceptible genes that contributes to maintenance of self tolerance (certain LHA genotypes occur more frequently in ppl with AI disorders)
- could be environmental factors (infections)
What 4 environmental factors can influence autoimmune disease? Describe what each is
1) . Breakdown of T cell anergy (when lymphocyte is functional inactivated following an antigen encounter)
2) . release of sequestered antigens-release of self-antigen after being hidden in development will be regarded as foreign
3) . Molecular mimicry: microbe shares immunologic epitope with host (ex pericarditis usually develops after renal strep infection; epitopes on pericardial sac are similar to strep antigen)
4) . superantigens: staph and strep exotoxins that short circuit the normal events in an immune response
How do you diagnosis an autoimmune disorder? (suggested criteria vs clinical findings/testing)
suggested criteria: evidence of autoimmune rxn, immunologic findings aren’t secondary to another disorder, lack of other identifiable cause
Clinical findings/testing: demonstration of ABs against tissue antigens or cell components
What is the treatment for an autoimmune disease based on? What are the first two meds usually administered?
based on tissue or organ involved, effector mechanism involved, magnitude and chronicity of effector process
Corticosteroids and immunosuppressive drugs administered first and then plasma exchange therapy
What is happening during transplant rejection and what are the specific antigens that make the determination?
Recipients immune system recognizes the graft as foreign and attacks it
HLA recognizes graft as foreign
What are autologous, syngeneic, and allogeneic grafts?
autologous: donor and recipient are the same (ex: skin graft from yourself)
Syngeneic: donor and recipient are identical twins
Allogeneic: donor and recipient are related or unrelated but share HLA types
What type of immunity does transplant rejection involve?
Cell-mediated immunity and circulating ABs
T cells IMPORTANT
What are the two pathways by which T lymphocytes recognize allogenic antigens? Describe what happens during them
Direct Pathway- T cells of recipient recognize allogenic MHC on surface of APCs in the graft; CD4 and CD8 involved and kill graft cells
Indirect Pathway- recipient CD4 cells recognize donor MHC molecule after they’ve already been processed on recipient’s APCs; activates DTH pathway (type IV hypersensitivity rxn) so ABs are produced against graft
What are the three transplant rejection reactions?
Hyperacute, acute, and chronic
What is the hyperacute rxn during transplant rejection?
occurs immediately (hrs or days) most common in kidney transplants existing recipient AB attack graft antigens and initiate type III hypersensitivity rxn in graft BVs
What is the acute rxn during transplant rejection
Occurs in first few months
activated T cells cause direct lysis of graft cells and recruit/activate inflammatory cells that injure graft
What is the chronic rxn during transplant rejection
occurs over prolonged period (years)
can see dense intimal fibrosis of BVs in transplant graft
mechanism is unclear (may be cytokines)
What is graft versus host disease? (GVHD) When is it most common? what cells are attacking and what type of rxn does this provoke?
immune competent cells are transplanted into recipients who have a compromised immune system
Most common after BM or liver transplant
Donor CD4 and CD8 T cells are activated and attack recipient (type IV hypersensitivity rxn)
What is acute vs chronic GVHD?
Acute- epithelial cells of skin, liver, GI tract (skin is most affected); creates rash on palms and soles
Chronic- develop skin lesions resembling systemic sclerosis or other AI disorder symptoms
What two types of cells can have problems in them that lead to immunodeficiency disorders?
B lymphocytes- humoral immunity
T lymphocytes and cytokines- cell mediated immunity
What is primary vs secondary immunodeficiency disorders?
primary- congenital or inherited; usually recessive traits on X chromosome
Secondary- acquired (like AIDS)
What are the three phases of HIV and CD4 count numbers?
Primary acute HIV infection- >500 (29%)
latency- 200-499 (12-28%)
overt AIDS- <200 (<14%)
What characterizes AIDS?
low CD4 counts
profound immunosuppression with signs of opportunistic infections
malignancies, wasting, CNS degeneration
What are the three types of opportunistic infections of AIDS?
Respiratory- bacterial pneumo (P jiroveci), pulm TB in HIV, CMV (cytomegalyvirus)
GI-herpes simplex, diarrhea and gastroenteritis, esophageal candidiasis
NS- cognitive disorders (HANDs), Toxoplasmosis
What is wasting syndrome in AIDS? What is it treated with?
involuntary weight loss of 10% of baseline body weight, diarrhea more than 2 stools/day, chronic weakness & fever
Oral supplements or parenteral nutrition
How do we currently treat HIV/AIDS?
combination therapy (at least three antiretroviral drugs) Nucleoside/tide reverse transcriptase inhibits, NonNRTIs, protease inhibitors, entry inhibitors, and integrase inhibitors
How do we reduce maternal transmission of AIDS?
maternal antivirals (zidovudine); reduce by 2/3rds
