7 immune system Flashcards
Hypersensitivity reaction definition
Altered immunologic reactivity to antigen –> pathologic immune response after re-exposure
Allergy definiition
Immunological hypersensitivty exogenous antigens (allergen)
How many types of hypersensitivty reactions are there
4
type I through IV
Type I HR
Allergic reaction, IgE mediated, immediate response
Most common form of allergic reaction
Ranges from mild to severe (anaphylaxis)
Type II HR
Tissue specific, cytotoxic, antibody mediated
Type III HR
Immune complex
Type IV HR
Cell mediated, delayed hypersensitivty
3 phases of type I HR
Sensitization of Mast and basophils
Initial-phase response
Late-phase response
Phase 1 of type I HR (sensitization of mast and basophils)
Exposure to allergen
Type 2 helper t-cells release cytokines in response followed by 2 important events
-B-Cell differentiation into plasma cells, IgE production (primary response)
-Eosinophil recruitment (secondary response)
Mast cells in tissue and basophils in bloodstream are then sensitized via addition of IgE to their cell membranes
Primary (initial) phase response Type I HR
Allergen binds to IgE causing degranulation of mast cells and basophils, which release pre-formed chemical mediators (histamine, acetylcholine, adenosine, chemotactic factors, kinins)
Response in 5-30 minutes, lasting 60 minutes
Vasodilation, increased cap perm, inflammation and smooth muscle contraction
Late-phase response in type I HR
Arachidonic Acid pathway, 2-8 hours later lasting several days
Mast cell/basophil cell membrane phospholipids breakdown into arachidonic acid which synthesizes leukotrienes and prostaglandins
Cytokines are released which cause influx/recruitment of eosinophils and leukocytes
Clinical manifestations of HR
Nausea/vomiting/GI cramps
Conjunctivitis, rhinitis, asthma, uticaria (white fluid filled blisters surrounded by erthema) hives
E.g asthma, hay fever, dermatitis (eczema) and anaphylaxis
Anaphylatic
Rapid and severe (within minutes of re-exposure)
Can be general or systemic
Hemodynamic compromise is key, due to presence within blood stream
Also major risk of upper/lower airway compromise
Type II HR reaction
Cytotoxic - tissue specific reactions
Characterized by destruction of a target cell
May be endogenous, or exogenous etiology
Through actions of IgG and IgM
Type II HR IgG and IgM
Tissue specific antigens cause
Cell destruction
Tissue inflammation
Cell dysfunction
Cell destruction by IgG and IgM in type II HR
Antigens targeted by IgG and IgM and are destroyed either by complement system or leukocytes
E.G transfusion reactions, rheumatic fever, RH incompatibility, certain drug reactions and transplant rejection
Tissue inflammation in type II HR by IgG and IgM
Antibodies in extracellular tissue (basement membrane or matrix) are deposited, leading to a complement mediated inflammation
Seen in renal disease and transplant rejection related to organ vasculature
Cell dysfunction in type II HR and IgG and IgM
Antibody mediated change in function of a given cell rather than destruction
E.g graves disease is TSH receptor binding causing overproduction of thyroixine leading to hyperthyroidism
Also Myasthenia gravis is destruction of ACH receptors at neuromusclular endplates
Type III HR
Immune complex mediated (IgG and IgM again)
Complexes ar formed in circulation, deposited later in vessel walls and extravascular tissue which cause compliment activation and neutrophils
Examples of type III HR
Arthus (localized inflammatory and tissue necrosis)
Immune complex lodged in vessels causing vasculitis
SLE
Polyarthitis nodosa
Type IV HR
Cell mediated destruction (not antibody mediated)
Carried out by sensitized t lymphocytes
Response to microorganisms, chemical antigens, self, transplants
Antigen presented by APC to helper t-lymphocytes (sensitized by helper T)
Direct or delayed
Direct cell mediated cytotoxicity (type IV HR)
Primary helper T cells directs T lymphocytes (CD8) to directly kill cells that express certain surface antigens
E.g viral hepatitis, destruction of hepatocytes is caused by cytotoxic t-lymphocytes rather than virus
poison ivy
transplant rejection
Delayed-type HR disorders (type IV)
Pre-sensitazaion of helper T lymphos (CD4) release cytokines upon re exposure leading to a delayed response by a number of inflamm cells causing cell damage
Examples of delayed type HR disorders
TB test, contact dermatitis (metal and latex) hypersensitivty pneumonitis and transplant rejection
*Type I name
IgE bound to mast cells release histamine and others
*Type I mechanism
IgE
*Type I examples
Seasonal allergic rhinitis, anaphylatic reactions
*Type II name
Cyotoxic/tissue specific reaction,
IgG and IgM bind to antigens of cells
*Type II mechanism
IgG and IgM
*Type II examples
Hemolytic anemia
Myasethenia Gravis
Transplant rejection
*Type III name
Immune complex mediated - deposited in tissues
*Type III mechanism
IgG and IgM
*Type III examples
Systemic lupus erythematous, polyarthris nodosa
*Type IV name
Cell mediated/ delayed reaction
*Type IV mechanism
T-lymphocytes
*Type IV examples
Contact sensitivty to poison ivy, metals, TB test, transplant rejection
Autoimmune disease overview
Represent a group of disorders when the body cannot identify self vs non self
MHC part of it, but there are other proteins/glycoproteins on our cells that are also recognized as self-antigens
Etiology of autoimmune
Largely unknown but there is a genetic predispositon and environvmental factors (triggering event interacts to precipitate the altered immune state) can be caused by infections, hormones, toxins
Breakdown of t-cell anergy in autoimmune
Anergy is a state of unresponsiveness to antigens when t-cells encounter our self antigens
MS and RA (or infection, tissue necrosis, inflammation) can cause certain tissue to release chemicals to cause breakdown of t-cell anergy
Hidden antigens autoimmune
Self-antigens are hidden and exposed later, then perceived as foreign
Molecular mimicry autoimmune
Microbe share an immunological epitope with the host. Body produces immune response to microbe’s epitope (acute glomeruloneephritis and RF)
Neoantigens autoimmune
Haptens bind to our tissue and create hapten adduct. Environmental chemicals or drug metabolites form these
Forbidden clone autoimmune
During normal T and B cell proliferation in the thymus the lymphocytes react to MHCs and are deleted. Sometimes they survive
Superantigens autoimmune
Infectious toxins that have ability to disrupt normal immune response process and create inappropriate activation of CD4 helper Ts which target our self antigens (food poisoning and chron’s)
Examples of systemic autoimmune disorders
RA, RF, SLE
Autoimmune of parietal cells (stomach)
pernicious anemia
Organ specific autoimmune
Hashimotos Graves IDDM Myasthenia Gravis Chron's and ulcerative colitis
SLE
Type III HR Chronic inflammatory disease Marked by remission/exacerbations Mutifactorial etiology (family) Mostly women between 20-40 UV light may trigger it
Patho of SLE
Large number of circulating antibodies against DNA, platelets, RBCs and nucleic acids
Immune complexes deposited in CT anywhere, activating complement and causing inflammation and necrosis
Vasculitis in many organs
Areas of SLE
Kidneys (lupus nephritis) lungs heart brain skin GI
Diagnosis based on minimum 4 areas
Clinical manifestations of SLE
Most common Arthalgia Fever Malaise Facial erythema (butterfly rash)
Other forms of lupus
Discoid (cutaneous) does not affect internal organs
Drug induced - symptoms disappear 6 months after stopping drug (or sooner)
Transfusion reaction is a
Type II HR
Immunogoblins in transfusion reactions
IgM (ABO)
IgG (Rh)
Person with antigen A have type A blood
ABO reactions (IgM)
Causes RBC agglutination and hemolysis
S&S of transfusion reactions
Heat along venous infusion site Flushed face headache uticaria fever and chills lower back pain chest pain abdo cramps N/V Tachycardia, hypotension, SOB Renal deficits
Rh incompatibility
Antigen present is Rh+
If Rh- pt receives Rh+ blood THEN the body will build up antibodies
Second transfusion with Rh+ blood is given
Hemolysis and severe reaction will occur
Pregnancy and Rh
Mother is Rh- and fetus is Rh+ creates incompatibility. First pregnancy is okay, but when placenta tears mom is exposed to Rh+ antibodies
Subsequent pregnancies Rh antibodies cross to fetus
Complications and treatment of pregnancy Rh incompatibility
Hemolysis, anemia, low Hb, high bilirubin, jaundice
Heart failure and death
Tx is Rh immunoglobuin to mother after first delivery which prevents sensitization
You have AIDS
HIV is causative agent
Aids is active stage
Can take 6-14 months to develop antibodies which can be detected
HIV positive for months to years before full blown AIDS
High risk for aids
Unprotected sex regardless of orientation
IV drug users
Hemophiliacs
So you have AIDS and you want to know the pathophysiology
Retrovirus (genetic info in form of RNA rather than DNA)
Binds to host cells surface and inserts RNA which is converted to DNA into hosts material
CD4 on surface of t-helper acts as receptor. Virus kills t-helper and the immune system is compromised
Phase one of AIDS
Phase 1 is initial infection and development of antibodies
Self limiting and flu-like S&S
Phase two of AIDS
Latent period, virus is hiding. Virus has mutated or crippled specific immunity against it
Usually asymptomatic, may have lymphadenopathy
Phase three of AIDS
Low CD4+ levels.
All the bad stuff happens
Generalized manifestations of AIDS
Lymphadenopathy, fatigue/weakness, headache, GI effects (severe diarrhea, vomting, ulcers), severe weight loss
Neuro (AIDS dementia) from infection of brain cells
Secondary infectioons (herpes, candida, pneumocystis carinii)
Treatment for AIDS
Treatment with antiviral drug azidothymidine (AZT)
Organ transplant overview
Cells, tissue or organs all referred to as grafts
Self = autologous
Identical Twin = syngeneic
Related = allogenic (genetically different)
Unrelated = allogenic
Immunosupprsents are used (Cyclosporine, AZT, prednisone)
MHC
Major histocompatibility complex AKA HLA human leukocyte antigen
Group of genes found on chromosome 6. Closer the antigen match the less rejection
Pathogenesis of tissue rejection
Cell mediated rejection usually
T-cells type IV HR can be direct or delayed
May be humoral medaited type 2/3 HR
Hyperacute clinical manifestations of tissue rejection
Antibody mediated, occurs in minutes
Previous tranfusions, transplants or pregnancy lead to development of target antibodies that attack donor tissue.
Usually type II or III HR
Often in vascular areas
Acute clinical manifestations of tissue rejection
T cell mediated in days to months
Direct or delayed lysis and inflammation of tissue
Chronic clinical manifestations of tissue rejection
Idiopathic
Months to years
Fibrotic changes in tissue
