IgG
Most abundant
Crosses the placenta
Remains in circulation after infection is gone
IgA
found in mucous membranes and secretions
IgM
First to appear in response to antigen
IgD
Found on B cells
Required for maturation
IgE
Inflammation, allergic responses, parasites
(Eosinophils)
Binds to a mast cell signaling the release of histamine
Type 1 hypersensitivity
IgE mediated- binds to mast cells to signal release of histamines
Espies allergic reactions
Local (rhinitis) or systemic (anaphylaxis)
Reaction is worse each time due to antibodies being made
(A in acid for Allergies and Anaphylaxis)
Phase 1. Vasodilation
Type 2 hypersensitivity
Cytotoxic/Antibody mediated by IgG or IgM against the target
Antibody binds to cell surface of antigen or complement (blood transfusion reactions)
Antibody on cell surface stimulates inflammation (glomerulonephritis, goodpasture's syndrome)
Antibody binds
Type 3 hypersensitivity
Immune complex mediated
Antibody/antigen complexes form and circulate
Come into contact with vessel or tissue they stimulate the inflammatory response (complement, neutrophils,inflammatory mediators)
Systemic lupus erythematosus
Glomerulonephritis
(I in a
Type 4 hypersensitivity
Cell mediated by sensitized T lymphocytes
T cells destroy all virus containing cells or
CD4 cells secrete cytokines initiating the inflammatory response
(D in acid is for delayed reaction)
Ex. Contact dermatitis (poison ivy, Nickel)
After initial exposure
Acute Transplant rejection/ direct pathway
APCs come from the donated tissue
Host T cells recognize foreign MHC molecules
CD8 cells recognize foreign MHC molecules and kill the foreign tissue
CD4 cells secrete cytokines to increase vascular permeability and accumulate macrophages
Happens within mo
Graft v Host Disease occurs when
Cells with a functional immune capacity are transplanted into someone who is immunocompromised and the donor tissue attacks the host (t cells)
The donor tissue must have a functional immune component ( bone marrow)
Recipient must have antigens much differ
Chronic transplant rejection/ indirect pathway
Donor antigens & their MHC molecules are processed and presented to T cells by host APCs
T lymphocytes do their 3 things
Antibodies may be involved especially is there was a precious ABO mismatch or donor rejection
Gradual failure of the organ
systemic lupus erythematosus
B cell hyperactivity and increased production of auto-antibodies
Antibodies cause direct damage to tissue, and combine with antigens to form tissue damaging immune complexes
Believed to be triggered by UV light, chemicals, foods or infectious agents
Cardinal signs of inflammation
redness, swelling, heat, pain, loss of function
Inflammatory cells: leukocytes (NLMEB)
Neutrophils: phagocytic, secrete toxic oxygen to attack pathogens, arrive early
Lymphocytes: b and T cells
Macrophages: clear tissue debris, secrete cytokines, inflammatory mediators and growth factor
Eosinophils: secrete mediators in response to allergie
Basophils/ mast cells
Secrete histamine and tumor necrosis factor
Histamine
Inflammatory mediators secreted by basophils/ mast cells
Vasodilation
Increased permeability to allow WBC movement to the area
Prostaglandins
Type of Arachidonic Acid Metabolite
Created through the COX pathway
Potentials histamines and induces imflammation
Leukotrines
Arachidonic Acid Metabolite
Made through the Lipoxygenase pathway
Takes over for histamine (vasodilation, increased vascular permeability, attraction of inflammatory cells, smooth muscle contraction)
Tumor Necrosis Factor and Interleukins
Cytokines
Induce endothelial cells to express adhesion molecules
Release other cytokines
Release toxic oxygen
Induce acute -phase response of systemic inflammation (fever, increased HR, increased neutrophils, increased corticosteroids)
Nitric Oxide
Inflammatory mediator
Smooth muscle relaxation and vasodilation
Oxygen free radicals as inflammatory mediators
Increase expression of cytokines
Vascular changes in acute inflammation
Vasoconstriction followed by vasodilation induces by histamine and nitric oxide
Increased vascular permeability (vasodilation causes gaps between the cells to form, protein rich exudate moves into the extravascular space, increased osmotic pressure to pul
Types of exudates
Serous - watery fluid
Sanguinous/Hemorrhagic- bloody
Fibrinous- contains fibrinogen
Purulent- contains pus
Cellular changes in Acute Inflammation
Margination- epithelial cells release cytokines and attract leukocytes at the site of injury
Adhesion- cytokines stimulate endothelial cells to express adhesion molecules which will tether the leukocytes. The leukocytes will roll across these adhesion mol
Chronic Inflammation
Characterized by infiltration of macrophages and lymphocytes
Fibroblasts leave instead of protein rich exudates
Caused by persistent infections or irritants that do not spread rapidly
Ex. Granulomatous - associated with foreign bodies and some microorgani
Systemic Inflammation
Systemic response from release of inflammatory mediators into circulation
The acute phase response occurs throughout the body leading to anorexia, sleepiness, can lead to systemic inflammatory response syndrome ( leads to an MI)
lymphadenitis
Reaction in the lymph nodes when inflammatory mediators are drained into them
Painful palpable lymph nodes
Tissue regeneration
Replacement of damaged tissue with the same cell type.
Parenchymal cells: functional ( less chance of scar)
Stromal cells: supportive ( more likely to scar)
Cell types for regeneration
Labile:constantly regenerate (skin)
Stable: stop dividing, but can regenerate if signaled (liver)
Permanent: do not regenerate (neurons of CNS or myocardium)
Fibrous tissue repair
Replacement of damaged tissue with connective tissue.
Usually occurs with severe or repeated injury to both parenchymal and stromal tissue
3 steps of Fibrous Tissue Repair
Generation of granulation tissue: moist red connective tissue, angiogenesis, foundation of new tissue
Fibrogenesis: influx of fibroblasts lay down ECM made from proteoglycans (responsible for swelling)
Scar formation: fibroblasts increase collagen synthes
Keloid scar
Raised scar due to excess collagen production
Genetic predisposition
Prevalent among African Americans
Primary intention
a sutured wound, minimal tissue loss, heals quickly
Secondary intention healing
Tissue heals on its own.
3 phases of wound healing process
1. Inflammatory: prepares the wound for healing
2. Proliferative: growth factor, angiogenesis, epithelial cells are produced at the wound edge, granulation tissue
3. Remodeling: materials are reabsorbed and wound shrinks in on itself
Prions
Protein particles (mutation of normal host protein)
Cause non-inflammatory degeneration of neurons
Ex Creutzfeldt-Jakob disease; Mad Cow Disease
Viruses
Composed of protein coat and nucleus acid core
Need a host to replicate
Can insert themselves into a host genome and stay dormant for years
Ex. Heroes simplex, varicella zoster, cytomegalovirus, Epstein Bar, HpV, HIV
HIV
A retrovirus that attacks CD4 cells
Can lead to AIDs
Profound suppression of immune system
Opportunistic infections
Malignancy
Body wasting
CNS degeneration
HIV Window Period
Contagious even though they have no symptoms
Mechanism behind HIV
Reverse transcriptase creates DNA from viral RNA by using the organelles in CD4 cells
Viral DNA is incorporated into the host cell
Codes for viral proteins which can create new virus cells
Bacteria
Unicellular
No nucleus- have both DNA and RNA
highly adaptable
Rickettsiaceae and Chlamydiaceae
Organisms that combine characteristics of viruses and bacteria (need a host to replicate, contain DNA and RNA)
Rickettsiaceae is transmitted by arthropod bite( Rocky Mountain spotted fever)
Chlamydiaceae is transmitted directly
5 stages of infection
1. incubation- slow replication, no symptoms
2. prodromal- appearance of constitutional symptoms
3. acute- max replication, max symptoms, inflammatory and tissue damage
4. convalescent- containment of pathogen, tissue repair, resolution of symptoms
5. rec
3 steps of normal hemostasis
1. Vessel spasms- constriction to decrease blood flow, dilation to increase WBC travel to area
2. Formation of platelet Plug - vWF & fibrinogen
3. Coagulation cascade
Coagulation Cascade: Intrinsic Pathway
Longer process and slower
Heparin
PTT
Fibrin is the end product
Calcium acts as a coenzyme
Blood or vessel injury
Fibrinolysis
Plasminogen becomes plasmin
Plasmin digests the fibrin strands and clotting factors
TPA
Medication that stimulates fibrinolysis and breaks down clots
Primary Thrombocytosis
Abnormally high levels of free thrombopoietin due to abnormal receptors on platelets.
Thrombopoietin cannot bind/see to the platelets and signals the marrow that there aren't enough platelets in circulation
Increased risk for clot
Secondary Thrombocytosis
Increased production of thrombopoietin due to tissue damage
Common after surgery, infection, cancer, inflammatory disease
coagulation cascade: extrinsic pathway
Shorter process and faster
Warfarin/Kumadin
PT
Tissue factor
Factor V Leiden mutation
Inherited hypercoagulable state
Factor 5 is not shut off and the coagulation cascade can not be stopped.
Prothrombin gene mutation
Elevated prothrombin levels causes increased stimulation of the end of the cascade
hereditary deficiencies in protein C, S or antithrombin 2
Hyper-coagulable state
Cannot turn off the coagulation cascade
Hyper coagulable states caused by acquired disordeer
1. Blood pooling due to immobility
2. MI- back up of blood
3. Hyper-estrogenic states/ hormone based contraceptives- increased synthesis of clot factor reduced synthesis of antithrombin 3
Thrombocytopenia
Reduced number of platelets
Risk of bleeds
Heparin-Induced Thrombocytopenia
Pt must be taking heparin
There is an immune reaction against the heparin-platelet factor 4 complex
Platelets are being used to go after the complex resulting in fewer serum platelets
Immune Thrombocytopenic Purpura (ITP)
Autoimmune
Antibodies are made against the 2N3A platelet receptor.
The platelet becomes surrounded by antibodies making it susceptible to phagocytosis and removal by the spleen
Thrombotic Thrombocytopenic Purpura (TTP)
Deficiency of enzyme that degraded vWF
Platelets will adhere to the non-useable vWF
Decreased blood serum platelet count
The chains of vWF covered with platelets can get stuck in capillaries leading to a thrombi
Eliminated by the spleen or phagocytosis
How do ASA and NSAIDs cause impaired platelet function?
Decreased activity of the COX pathway leading to less prostaglandins ( less inflammation)
Decreased production of thromboxane, which decreases platelet aggregation (risk of bleeding)
Hemophilia A
Coagulation factor deficiency
1/5000 male live births
Genetic factor 8 deficiency (impacts coagulation cascade)
Hemophilia B (Christmas disease)
Genetic factor 9 deficiency
Cannot make fibrin
Von Willebrand Disease
1/1000 people
Genetic deficiency or defect in vWF
Platelets cannot adhere to subendothelium
Why is liver failure considered a bleeding disorder?
Many clotting factors are made by the liver
Liver disease results in the reduction of these leading to no initiation of the coagulation cascade
Disseminated Intravascular Coagulation (DIC)
When there is a large injury or widespread coagulation and bleeding, there is a large activation of the coagulation response and a massive clot forms that consumes all available clotting supplies
This is followed by a bleed out because there are no more r
Sickle cell anemia
Abnormality in hemoglobins S synthesis
Most common in African Americans
Deoxygenation and dehydration causes a sickle cell
Hemolysis
Pt will feel fatigued
Provides resistance against malaria
Thalessemia
Disorder of hemoglobin synthesis
Results in pale and small RBCs
Accumulation of unaffected chains results in early hemolysis
2 types: alpha and beta
Alpha- common in Asians
Beta- common in Mediterranean's (Italy and Greece)
BOTH are common in African Amer
iron deficiency anemia
Most commonly caused by a bleed because most of our iron is recycled from old RBCs
Lack of iron impedes hemoglobin production
Could also be dietary
Vitamin B12 deficiency anemia
B12 is essential for DNA synthesis
Usually dietary
Strict vegetarians and vegans most commonly
Large cells with a short life span grow
Folic acid deficiency anemia
Folic acid is required for DNA synthesis and RBC maturation
Dietary - anyone who doesn't eat green leafy vegetables
Neutropenia
Low neutrophil count
Can be congenital
Most often it's acquired- autoimmune response against neutrophils, overuse due to systemic infection, drug related (chemo therapy kills good cells too)
infectious mononucleosis
caused by the Epstein-Barr virus
Spreads by oral secretions
Binds to B cells
Virus either kills the host or implants itself in the DNA
Antibodies are easily detectable for diagnosis
Non-Hodgkin's Lymphoma
Commonly in the B cells ( can also be T)
Originate in the lymph nodes or extranodal sites
More peripheral
Spread is not contiguous ( not in a line)
Extranodal involvement is common
Signs: swollen and painless nodes
Constitutional symptoms of tiredness, fa
Hodgkin Lymphoma (HL)
Arises from a single. Ode or chain of nodes typically confined to the head or neck.
Spreads to whatever lymph node is closest
Reed-Sternberg cell: mirrored nucleus
Most common in people younger than 40 and adults over 55
Signs: painless enlargement of a s