Immunology- Immune Phase Reactants Flashcards
Acute phase reactants
Factors whose serum concentrations change in response to inflammation
Produced by the liver
Induced by IL-6
C reactive protein
Note: not to be confused with protein C (coagulation cascade) or C-peptide (component of proinsulin)
Opsonin: fixes complement and facilitates phagocytosis
Clinically: used to assess ongoing inflammation
Ferritin
Binds and sequesters iron to inhibit microbial iron scavenging
Fibrinogen
Coagulation factor (1); promotes endothelial repair; correlates with ESR
Hepcidin
Decreases iron absorption by degrading ferroportin and decreasing iron release from Mphages
elevated in anemia of chronic disease
Serum amyloid A
Prolonged elevation can lead to amyloidosis
Factors that are DOWNregulated
Albumin- AAs are being used to make the unregulated reactants (CRP, ferritin, fibrinogen, hepcidin, and serum amyloid A)
Transferrin- internalized by Mphages to sequester iron
Complement
Hepatically synthesize plasma proteins that play a role in innate immunity and inflammation; MAC defends against gram - bacteria
Classic pathway
Mediated by IgG and IgM (GM makes CLASSIC cars)
Alternative pathway
Microbe surface molecules
Lectin pathway
Mannose or other sugars on microbe surface
C3b- role
opsonization; binds bacteria
C3a, C4a, C5a
anaphylaxis
C5a (also)
neutrophil chemotaxis
C5b-C9
cytolysis by MAC
Opsonins
C3b and IgG; enhance phagocytosis
C3b also helps clear immune complexes
Inhibitors (of complement)
decay-accelerating factor (DAF– aka CD55) and C1 esterase inhibit complement activation on self- cells (e..g RBCs)
C1 esterase inhibitor deficiency
Can cause hereditary angioedema (unregulated activation of kallikrein –> increases bradykinin)
ACE inhibitors are CONTRAINDICATED
C3 deficiency
Increases risk of severe, recurrent pyogenic sinus and respiratory tract infections; increased susceptibility to type III HS reactions (more things have to go down the adaptive pathway)
C5-C9 deficiency
MAC complex
Increases susceptibility to Neisseria infections/ bacteremia
DAF- GPI-anchored enzyme deficiency
Causes complement-mediated lysis of RBCs
Paroxysmal nocturnal hemoglobinuria
IL-1- secreted by Mphages
Aka osteoclast activating factor
“Hot”: causes fever
Produced by mononuclear phagocytes and stimulates WBC recruitment
IL-2- secreted by ALL T cells
“T”: Stimulates growth of ALL T cells + NK cells
IL-2 administered in melanoma to increase host NK response (and adaptive immune response- T cells)
IL3- secreted by ALL T cells
“Bone”: supports growth of bone marrow stem cells (like GM-CSF– stimulates stem cell prod of granulocytes and monocytes)
IL-4- secreted by Th2 cells
“E”: Induces differentiation of T cells in Th2 cells
Promotes growth of B cells and IgG and IgE class switching
IL-5- secreted by Th2 cells
“A”: Promotes growth and diff of B cell- enhances class switching to IgA
Stimulate growth and diff of eosinophils
IL-6- secreted by Mphages
“K”: Produces a”K”ute phase reactants and causes fever
IL-8- secreted by Mphages
“Clean up on aisle 8”
Chemotactic factors for neutrophils (like C5a, and LT B4)
Il-10- secreted by Th2 and Treg
A”ten”uates: Attenuates immune response (along with TGF- B)
Decreases expression of MHC Class II and Th1 cytokines, Mphages, and dendritic cells
IL-12- secreted by Mphages
Stimulate differentiation in Th1 cells; activates NK cells
TNF-alpha- secreted by Mphages
Mediates septic shock, activates endothelium, and causes WBC recruitment and vascular leak
Causes cachexia in malignancy
IFN-gamma- produced by Th1 and NK cells
Stimulates Mphages to kill phagocytosed pathogen
Inhibits Th2 differentiation
Also activates NK cells to kill virus-infected cell
Increases MHC expression and antigen presentation on ALL cells
Respiratory burst
Activation of phagocyte oxidase complex (in neutrophils and monocytes)
NADPH: plays a key role in creating and neutralizing the ROS
Myeloperoxidase: blue-green heme-containing pigment that gives sputum its color
Lactoferrin
Protein found in secretory fluids and neutrophils that inhibits microbial growth via iron chelation
IFN alpha and beta
Part of innate host defense against RNA and DNA viruses (interferons “interfere” with viruses)
Prime locally uninfected cells to selectively degrade viral nucleic acid
All nucleated cells
MHC I
RBCs dont have this though- makes sense because they are not nucleated!
T cells
TCR (binds antigen-MHC complex)
CD3 (signal transduction)
CD28 (binds to B7 on APC)
CCR5- on macrophages (early)/ CXCR4 (late)- on T cells (co-receptors for HIV)
Helper T cells
CD4, CD40L (used to bind to B cells)
Cytotoxic T cells
CD8, CXCR4/ CCR5
Regulatory T cells
CD4, CD25, FOXP3
B cells
Ig (binds antigen)
CD 19-21 (21- receptor for EBV), CD40 (used to bind to Th cells)
MHC II, B7 (used to bind to naive T cells)
Mphages
CD14 (receptor for PAMPs (e.g. LPS)), CD 40, CCR5, MHC II, B7, Fc and C3b receptors
NK cells
CD16 (binds Fc of IgG)
CD56 (unique for NK cells)
Hematopoietic stem cells
CD34
Anergy
State during wherein T cell is made refractory to any future stim (e.g. when antigen/MHC complex binds to TCR, but does not receive T cell does not receive costimulatory signal (e.g. from B7 (on APC) to CD28 (on T cell))
Superantigens
Can cross-like a region on the TCR to the MHC II of APCs thereby activating CD4+ T cells and causing massive release of cytokines
Endotoxins/ LPS
Directly stimulate Mphages (via binding to to CD14)
Passive vaccinations available for:
“To Be Healed Very Rapidly”
Tetanus Botulinum HBV Varicella Rabies
Live vaccines vs. inactivated vaccine
Live vaccine: induce cell-mediated (T cells) and humoral (antibodies) response (BCG, Influenza (intranasal), MMR, Polio (Sabin), Rubella, Varicella, Yellow Fever)
Inactivated vaccine: induces only humoral response (RIP Always- Rabies, H. Influenza, Polio, HAV)
Type I HS
Anaphylactic (bee sting, food allergies) and atopy (allergic hypersensitivity- rhinitis, asthma, eczema)
Antigen cross links IgE –> Fc binds mast cells and basophils –> histamine release (immediate) –> leukotrienes (delayed/ long-lasting effects)
Type II HS
Cytotoxic (antibody-mediated against our (normal) cells): AIHA, Goodpasture, Pernicious Anemia, ITP, Erythroblastosis fetalis, Rheumatic fever
Can also be complement-mediated (via opsonization and formation of MAC)
Direct vs. Indirect Coombs
Direct: Tests tissue (and looks for antibody deposits)
Indirect: Tests serum for antibodies
Type III HS
Immune complex mediated: Arthus reaction, SLE, Polyarteritis nodosa, PSGN, serum sickness
Arthus reaction
Immune complex formation in the skin after internal injection of antigen to pre-sensitized (individual has IgG) individual
Serum sickness
immune complex disease in which antibodies to foreign proteins are produced (takes 5 days)
Immune complexes deposit in tissue and fix complement (therby causing tissue damage)
Type IV HS
Delayed (T-cell mediated) HS (Transplant rejection, poison ivy/ contact dermatitis, TB test, MS)
Sensitized T cells encounter antigen and release cytokines and activate Mphages
Blood transfusion reactions- allergic rxn
Type I; caused by plasma proteins in blood
S&S: urticaria, wheezing, pruritis
Tx: antihistamines
Blood transfusion reactions- anaphylaxis
Can be seen in people with IgA deficiency
S&S: dyspnea, brochospasm, hypotension, respiratory arrest, shock
Tx: epinephrine
Blood transfusion reaction- febrile non-hemolytic
Type II HS; antibodies agains donor HLA antigens and WBCs
S&S: fever, headache, chills, flushing
Blood transfusion reaction- acute hemolytic
Type II HS; Intravascular hemolysis (donor RBCs themselves): ABO blood group incompatibility Extravascular hemolysis (foreign antigen on donor RBCs): host antibody reaction against foreign antigen on donor RBCs
S&S:
Intravascular: fever, hypotension, tachypnea, tachycaria, hemoglobinuria (can look like ATN, but will be preceded by TRANSFUSION)
Extravascular: jaundice
