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1st Aid: Immunology
Question | Answer |
---|---|
3 area of Lymph node | Follicle; medulla; paracortex |
Functions of lymph node | nonspecific filtration by macrophages, storage and activation of B and T cells, antibody production |
Describe the lymph node area: follicle | site of B cell localization and proliferation. Located in outer cortex. |
Differentiate the primary and secondary follicles of the lymph nodes | Primary: dense and dormant; Secondary: pale central germinal centers and active |
Describe the lymph node area: Medulla | Has medullary cords (pakced lymphocytes and plasma cells) and medullary sinuses. Sinuses communicate with efferent lympjhatics and contain reticular cells and macrophages |
Describe the lymph node area: paracortex | houses T cells. between follicles and medulla. |
What part of lymph node enlarges in an exremem cellular immune response? | Paracortex |
What area of the lymph node is not well developed in patients with DiGeorge Syndrome? | Paracortex |
Drains upper limb and lateral breast | axillary lymph nodes |
Lymph node draining stomach | Celiac |
Lymph node draining duodenum/jejunum | Superior Mesenteric |
Lymph node draining sigmoid colon | colic--inferior mesenteric |
Lymph node draining rectum and anal canal | internal iliac |
Lymph node draining anal canal below pectinate line | Superificial inguinal |
lymph node draining testes | superficial and deep plexuses--para aortic |
Lymph node draining scrotum | superficial inguinal |
Lymph node draining thigh superficially | Superficial inguinal |
Lymph node draining the lateral side of the dorsum of the foot | popliteal |
Right lymphtic duct drains? Thoracic duct drains? | Right arm/chest/half of head; everything else |
Where are T cells found within the spleen? | Within the periarterial lymphatic sheath (PALS) within the white pulp of the spllen |
Where are B cells found in the spleen? | In follicles within the white pulp of the spleen (inner layers) |
How does splenic dysfunction lead to increases suspetibility to encapsulated organisms? | Decreased IGM---Dec complement activation--- dec C3b opsonization--inc susceptibility |
What organisms are you more suseptible to with splenic dysfunction? | Encapsulated organsims (SHiN SKiS): Strep, H. influenza type B, Neisseria meningitidis, Salmonella, Klebsiella pneumoniae, group B Streptococci |
What is the site of T cell differentiation? | Thymus |
From what is the thymus developmentally derived? | epithelium of the 3rd branchial pouch |
What is in the cortex of the thymus? Medulla? | Cortes: dense immature T cells; Medulla: pale with mature T cells and epithelial reticular cells containing Hassall's corpuscles |
Where does positive (MHC restriction) and negative selections (nonreactive to self) occur respectivley for T cells | Positive: Cortex of thymus; Negative: medulla or thymus |
components of innate immunity? | neutrophils, macrophages, dendritic cells, natural killer cells (lymphoid origin), Complement |
Components of Adaptive Immunity? | T cells, B cells, Circulating Antibody |
What encodes major histocompatibility complexes? | HLA (human leukocyte antigen) |
HLA for MHC I | HLA-A; HLA-B; HLA-C |
MHC I binds? | TCR and CD8 |
MHC I is expressed by? | all nucleated cells (not RBCs) |
MHC I mediates? How? | Viral immunity; antigen loading in the RER with intracellular peptides |
What does MHC I pair with to be expressed on the cell surface? | B2 microglobulin |
HLA for MHC II | HLA-DR, HLA-DP, HLA-DQ |
MHC II binds? | TCR and CD4 |
MHC II expressed on? | only on APCs |
How is antigen loaded on MHC II? Does it bind large or small peptides? | antigen loaded following release of invariant chain in an acidified endosome; Large peptides (hot dog shaped groove) |
HLA-A3 disease? | Hemochromatosis |
HLA-B27 diseases? (4) | PAIR: psoriasis, Ankylosing spondylitis, Inflammatory bowel disease, Reiter's Syndrome |
HLA DQ2/DQ8 disease? | Celiac Dz |
HLA DR2 diseases? | MS, hay fever, SLE, Goodpastures |
HLA DR3 diseases? | Diabetes mellitus type I, Grave's disease |
HLA DR4 diseases? | RA; diabetes mellitus type 1 |
HLA DR5 diseases? | Pernicious Anemia--B12 deficiency, Hashimoto's Thyroiditis |
Describe teh action of Natural Killer Cells? | Use perforin and granzymes to induce apoptosis of virally infected cells and tumor cells |
What cell's activity is enhanced by IL2, IL1, IFNB, and IFN a? | Natural Killer cells |
What triggers the action of Natural Killer cells? | when exposed to nonspecific activation sinal on target cell and/or absence of class I MHC on target cell surface |
Antibody associated with Type I hypersensitivty? | Allergy: IgE |
Ab associated with Type II and Type III hypersensitivity reactions? | Cytotoxic and Immune Complex: IgG |
Activites of Antibodies? | Opsonization, neutralization (IgG), activate compliment (IgM, IgG), sensitize mast cells (IgE) |
What mediates Type IV hypersensitivity rxns? | Delayed cell-mediated: T cells |
What mediates Hyperacute organ rejections? | Antibodies (B cells0 |
What action ensures survival of T cells during positive selection in the thymic cortex? | T cells expressing TCR bind surface self MHC molecules |
How does negative selection of T cells occur in the medulla of the thymus? | T cell expressing TCRs with high affinity for self antigens undergo apoptosis |
Describe naive T cell activation | foreign body phagocytosed by dendritic cell--presented on MHC II to Th cell and MHC I to Tc cell (signal 1); Costimulatory signal with B7 and CD28 (signal 2); cytokines and cell killing action |
Describe B cell activation and class switching | Th cell activated--B cell receptor mediated endocytosis and MHC II presentation to TCR on Th (Signal 1); CD40 receptor on B cell binds CD40 ligand on Th cell (Signal 2)--cytokines determine Ig class switching, activation-switching, afinity maturation, Abs |
Th1 cells secrete? | IFN y |
Th2 cells secrete? | IL4,5,10,13 |
Th1 cells do? | activate Macrophages (IFN-y) |
Th2 cells do? | recruit eosinophils for parasite defense and promote IgE proudction by B cells |
Th1 cells inhibited by? | IL4,10 |
Th2 cells inhibited by? | IFNy |
Function of Regulatory T cells? | Suppress CD4 and CD8 Tcells by producing IL10 and TGF-B antiinflammatory cytokines |
CD3 , CD4, and CD25 are expressed on? | T reg cells |
What potion of Ab fixes complement? | Fc portion of IgM and IgG |
Do heavy chains contribute to Fc or Fab fractions of Ab? | both |
What poriton of the Ab determines its idiotype? | Fab |
4 C's of Fc fragment? | Constant, Carboxy terminal, Complement binding (IgM and IgG), Carbohydrate side chains |
What portion of b determines its iso type? | Fc |
How is diversity granted to Ab's? | Random recombination of VJ (light) and VDJ (heavy) genes; random combos of heavy chains with light chains; somatic hypermutation (follows antigen stimulation); addition of nucleotides to DNA during recombination by terminal deoxynucleotidyl transferase |
What isotypes do mature lymphocytes express? | IgM and IgD on surface |
Most abundant Ab isotype? function? | IgG; fixes complement, crosses placental barrier (passive immunity), opsonizes bacteria, neutralizes bacterial toxins and viruses |
IgA functions? | prevents attachement of pathogens to mucous membranes; secreted as dimer and crosses via trancytosis |
IgA acquires secretory component where? | from epithelial cells before secrteion |
Ab in primary response to antigen? Secondary? | IgM; IgG |
Does IgM cross placenta? | no; IgG does |
IgM shape? | pentamer (helps with trapping) |
IgE function? hypersensitivity rxN? | Binds mast cells and basophils with crosslinking when exposed to allergen; Type I (allergy) released of histamine and other mediators |
Thymus independent antigens lack what? | peptide component, cannot be presented by MHC (LPS from gram neg bacteria and polysaccharide capsular antigne) |
Immunological memory results from Thymus Independant or Dependent antigens? | Dependent |
What mediates the classical Complement pathway? Alternative path? Lectin Pathway? | IgG or IgM; microbe surface molecules; mannose or other sugars on microbe surface |
C3b function? | opsonization and clearing of immune complexes |
What complement components function in anaphylaxis? | C3a, C5a |
C5a functions? | anaphylaxis and neutrophil chemotaxis |
C5b-9 function? | cytolysis by MAC |
two primary opsonins in bacterial defense? | C3b and IgG |
Dz where C1 esterase inhibitor is deficient? What meds are contraindicated? | Hereditary Angioedema; ACE inhibitors |
C3 deficiency can result in two diseases/conditions | Sever, recurrent pyogenic sinus/resp tract infections; increase suspetibility to type III hypersensitivity reactions |
Recurrent Neisseria bactermia can result from what specific immune deficiency? | C5-C9 def |
Decay accelerating Factor (DAF) deficiency can result in? | complement mediated lysis of RBCs and paroxysmal nocturnal hemoglobinuria (PNH); DAF is complement inhibitor |
Important cytokines secreted during inflammation (acute) | Hot T-Bone stEAk: IL1 (hot), IL2 (stimulates T cells), IL3 (stimulates bone marrow), IL4 (stimulates IgE production), IL5 (IgA production) |
IL-1? | endogenous pyrogen; activates endothlial adhesion molecules; recruit leukocytes (macrophages) |
IL-6? | Endogenous pyrogen; causes fever and stimulates Acute Phase Proteins (macrophages and Th2 cells) |
IL-8? | Major chemotactic factor for neutrophils (macrophages) |
IL-12? | Induces differentiation of T cells into Th1 cells; activates NK cells (macrophages and B cells) |
TNF-a? | mediates septic shock; activates endothelium; causes leukocyte recruitment and vascular leak (Macrophages) |
IL-2? | Stimulates growth of helper, Cytotoxic, and T reg cells (ALL T cells) |
IL-3? | Supports the growth and differentiation of bone marrow stem cells. Like GM-CSF (ALL T cells) |
IFN-y | activates macrophages and Th1 cells. Antiviral/antitumor properties? (Th1 cells) |
IL-4? | induces differentiation of Th2 cells; promotes B cell growth; enhances class switching to IgE and IgG (Th2 Cells) |
IL-5? | Promotes differentiation of B cells; enhances class switching to IgA; Stimulates growth of eosinophils (Th2 cells) |
IL-10? | Modulates inflammatory response; inhibits actions of activated T cells and Th1. (Th2 and Tregs) |
What do IFNs do in general? | place uninfected cells in antiviral state by inducing production of a ribonuclease that inhibits viral protein synthesis by degrading viral mRNA |
IFN a nd B have what antiviral effect? | inhibit viral protein synthesis |
IFN y have what antiviral effect? | Increase MHC I and II expression and antigen presentation in all cells |
Cell surface proteins of T cells | TCR (MHC-antigen), CD3 (TCR signal transduction), CD28 (B7 on APC) |
Cell surface proteins of Th cells | CD4; CD40 |
Cell surface proteins of Tc cells | CD8 |
Cell surface proteins of B cells | Ig; CD19; CD20; CD 21 (EBV receptors); CD40; MHC II, B7 |
Cell surface proteins of Macrophages | CD14, CD40, MHC II, B7; Fc and C3b receptors (enhanced phagocytosis |
Cell surface proteins of NK Cells | CD16 (Fc or IgG), CD56 (unique) |
Describe the action of superantigen toxins from S. pyogenes and S. aureus? | Crosslink B region of TCR to MHC II causing massive release of cytokines following from continous stimulation |
How do endotoxins/LPS affect immune system? | directly stimulate macrophages by binding endotoxin receptor CD14 |
Antigenic Variation in Salmonella? Borrelia? N. gonorrhoeae? | 2 flagellar variants, relapsing fever, pilus protein |
Antigenic Variation in influenza? | Antigenic shift (RNA/DNA reassortment) and Antigenic Drift (minor) |
Antigenic variation in trypanosomes? | programmed rearrangment |
For what diseases are passive immunity preformed antibodies commonly given? (4) | Tetanus Toxin; Botulinum Toxin; HBV; Rabies Virus |
For what diseases are combined passive and active immunizations given? | Hepatitis B and Rabies |
Kinds and examples of vaccines? | Live attenuated (measles/mumps/Sabin/rubella/varicella/yellow fever); Inactivate/Killed vaccine (Cholera/HepA/Salk/Rabies) |
What type of immunity is conferred by Live attenuated vaccine? Inactivate/killed vaccine? | Cellular response; Humoral Immunity |
Describe Type I hypersensitivity and tests for it? | Allergic/anaphylactic reaction after free antigen cross linking IgE on PRESENSITIZED mast cells or basophils which releases vasoactive amines; Skin test for specific IgE |
Describe Type II Hypersensitivity Rxn and tests for it? | Cytotoxic, Ab mediated destruction of a cell following binding of IgM or IgG (opsonization-phagocytosis, complement lysis, Ab-dep cell-mediated cytotoxicity from NK cell); direct and indirect Coombs |
Describe Type III Hypersensitivity Rxn and tests for it? | Immune complex-antigen-Ab (IgG) complexes activate complement which attracts neutrophils that release lysosomal enzymes; immunofluorescent staining |
What is serum sickness? | Type III rxn which Abs to foreing proteins are produced (5 days). Immune complexes form and deposit in membranes, where the fix complement |
What is Arthus reaction? | Local, subacute Type III reaction when intradermal injection of Ag induces Abs and forms immune complexes in the skin--edema, necrosis, activation of complement |
Describe Type IV Hypersensitivity Rxn and tests for it? | sensitized T lymphocytes encounter Ag and then release lymphokines (macrophage activation; NO Abs): 4 T's (T cells, Transplant rejection, TB skin tests, Touching (contact dermatitis); Patch Test, PPD |
Quickly categorize Hypersensitivity rxn | ACID: Anaphylactic (I), Cytotoxic-Ab mediated (II), Immune Complex (III), Delayed-cell mediated (IV) |
Type of Hypersensitivity Disorder: Anaphylaxis from Bee sting | I |
Type of Hypersensitivity Disorder: allergy | I |
Type of Hypersensitivity Disorder: Autoimmune Hemolytic Anemia | II |
Type of Hypersensitivity Disorder:Pernicious Anemia | II |
Type of Hypersensitivity Disorder:Idiopathic Thrombocytopenic Purpura | II |
Type of Hypersensitivity Disorder:Erythroblastosis fetalis | II |
Type of Hypersensitivity Disorder: Acute Hemolytic Transfusion reaction | II |
Type of Hypersensitivity Disorder:Rheumatic Fever | II |
Type of Hypersensitivity Disorder: Goodpasture Syndrome | II |
Type of Hypersensitivity Disorder: Bullous Pemphigoid | II |
Type of Hypersensitivity Disorder: Pemphigus Vulgaris | II |
Type of Hypersensitivity Disorder: SLE | III |
Type of Hypersensitivity Disorder: Polyarteritis Nodosa | III |
Type of Hypersensitivity Disorder:Post Strep Glomerulonephritis | III |
Type of Hypersensitivity Disorder:Serum Sickness | III |
Type of Hypersensitivity Disorder:Arthus Reaction (swelling following tetanus vaccine) | III |
Type of Hypersensitivity Disorder: MS | IV |
Type of Hypersensitivity Disorder: Guillain-Barre Syndrome | IV |
Type of Hypersensitivity Disorder: Graft-Versus Host Disease | IV |
Type of Hypersensitivity Disorder: PPD (TB test) | IV |
Type of Hypersensitivity Disorder: Contact Dermatitis (poison ivy) | IV |
Blood transfusion results in Urticaria, pruritus, wheezing, and fever. What is going on and how do you treat? | Type I allergic reaction against plasma proteins in transfused blood; Antihistamine |
Blood Transfusion results in Dyspnea, bronchospasm, hypotension, respiratory arrest and shock. What is happening? | Anaphylaxis following transfusion of IgA containing blood to an IgA deficient person |
Blood transfusion is followed by fever, headache, chills and flushing. They are experincing a Type II hypersensitivity reaction. What condition and how did it happen? | Febril nonhemolytic transfusion reaction where host Abs against donor HLA antigens and leukocytes |
Blood Transfusion followed by fever, hypotension, tachypnea, tachycardia, flank pain, hemoglobinemia (intravascular), jaundice (extravascular hemolysis). This is a TYPE II rxn. What condition and why? | Acute Hemolytic Transfusion reaction where intravascular hemolysis occurs from ABO blood goup incompatibility or extravascular hemolysis occurs from host Ab rxn against foreign Ag on Donor RBC |
SLE AutoAbs? | ANAs, Anti-dsDNA, Anti-Smith |
Drug induced lupus AutoAs? | Antihistone |
RA autoantibody? | Rheumatoid factor, Anti-CCP |
CREST Scleroderma autoantibody? | Anticentromere |
Diffuse Scleroderma autoAb? | Anti-Scl-70 (anti-DNA topoisomerase I) |
Primary Biliary Cirrhosis AutoAb? | Antimitochondrial |
Celic Disease AutoAb? | IgA antiendomysial, IA anti-tissue, Transglutaminase |
Goodpasture's Syndrome AutoAb? | Anti-Basement Membrane |
Pemphigus Vulgaris AutoAb? | Anti-Desmoglein |
Hashimoto's Thyroiditis AutoAb? | Antimicrossomal, Antithyroglobulin |
Polymyositis and Dermatomyositis AutoAb? | Anti-Jo-1, Anti-SRP, Anti-Mi2 |
Sjogren's syndrome AutoAbs? | Anti-SSA (anti-Ro); Anti-SSB (Anti-La) |
Autoimmune hepatitis AutoAb? | Anti-Smooth Muscle |
Type 1 diabetes mellitus AutoAb? | Anti-glutamate decarboxylase |
Granulomatosis with Polyangitis (Wegener's) AutoAb? | C-ANCA |
Churg-Strauss syndrome AutoAB? | p-ANCA |
With a T cell deficiency you would expect what bacterial effects? Viral? Fungi/parasites? | Sepsis; CMV/EBV/VZV/Chronic Resp virus; Candida, PCP |
With a B cell Deficiency you can expect what bacteria? Virus? Fungi/Parasites? | Encapsulated bacteria (SHiN SKiS); Enteroviral, Encephalitis, poliovirus; GI giardiasis |
With a granulocyte deficiency you expect what bacteria? Fungi/Parasites? | Staph, Burkholderia cepacia, Serratia, Nocardia; Candida, Aspergillus |
With Complement Deficiency you expect what bacterial infection? | Neisseria (no MAC) |
Recurrent bacterial infections after 6 months old as a result of opsonization defect. Normal Pro-B, dec maturation and number of B cells, dec Igs of all classes. Dz and defect | X-linked (Bruton's) agammaglobulinemia; X-linked recessive with defect in BTK (tyrosine kinase gene= no B cell maturation) |
IgA<7mg/dL with normal numbers of other isotypes; False positive B-HCG test due to presence of heterophile Ab; What Dz and what therapy is contraindicated in these people? | Selective IgA deficiency; Blood transfusion containing IgA |
Acquired in 20s-30s that grants increase risk of autoimmune disease, lymphoma and sinopulmonary infections. Normal number of B cells but decrease plasma cells and IgG | Common Variable Immunodeficiency; defect in B cell maturation |
Hyopcalcemia manifesting Tetany, recurrent viral/fungal infections, congenital heart and great vessel defects; Decreased PTH; absent thymic shadow on CxR | Thymic aplasia (Digeorge syndrome); 22q11 deletion; failure to develop 3rd and 4th pharyngeal pouch |
Disseminated mycobacterial infections with decreased IFN-y | IL-12 receptor deficiency; Decreased Th1 response |
Coarse Facies, cold (noninflamed), staphylococcal Abscesses, retained primary Teeth, increased IgE, Dermatologic problems (eczema); Increased IgE | (FATED): Hyper-IgE syndrome (Job's Syndrome); Th1 cells do not produce IFN-y neutrophils do not respond to chemotactic stimuli |
Failure to thrive, chronic diarrhea, thrush. Recurrent infections, absence of thymic shadow, germinal centers | SCI |
Triad of cerebellar defects (ataxia), spider angiomas, IgA deficiency; Increased AFP | Ataxia-telangiectasia; defects in ATM gene, codes DNA repair enzymes |
Severe pyogenic infections early in life with increased IgM; Decreased IgG, IgA and IgE | Myper-IgM syndrome; Most commonly defective CD40L on helper T cells=inability to class switch |
Triad of Thrombocytopenic purpura, INfections, and Eczema; Increased IgE, IgA; Decreased IgM | Wiskott-Aldrich Syndrome; X-linked, WAS gene on X chromosome with T cells unable to reorganize actin cytoseleton |
Defect in LFA-1 integrin (CD18) protein on phagocytes | Leukocyte adhesion deficiency (type 1) |
Recurrent pyogenic infections by staphylococci and streptococci; partial albinism, peripheral neuropathy; Giant Granules in neutrophils | Chediak_Higashi Syndrome (defect in lysosomal trafficking regulator gene (LYST); microtubule dysfunction in phagosome-lysosome fusion) |
What mediates Hyperacute transplant rejection | Ab (type II Rxn) from preformed donor antibodies |
What mediates Acute transplant rejection | Cell-mediated due to CTLs reacting against foreign MHCs |
What mediates Chronic Transplant rejection | Class I MHC (nonself) perceived by CTLS as class MHC I (self) presenting nonself antigen |
Cyclosporide MoA? | binds cyclophilins. This complex blocks the differentiation and activation of T cells by inhibiting calcineurin, thus preventing production of IL2 and its receptors |
Clinical indication for Cyclosporine? | selected autoimmune disorders and for supression of organ rejection |
Tacrolimus (FK-506) MoA | binds FK binding protein inhibiting calcineurin and secretions of IL2 and other cytokines |
Cyclosporine Toxicity? | nephrotoxic, HT, hyperlipidemia, Hyperglycemia, Gingival Hyperplasia, hirsutism |
Tacrolimus (FK-506) indication | potent immunosuppresant used in organ transplant recipients |
Tacrolimus Toxicity? | Nephrotoxic, HTN, hyperlipidemia, hyperglycemia, tremor |
Sirolimus (rapamycin) MoA | Inhibits mTOR. Inhibits T cell proliferation in response to IL-2 |
Sirolimus (rapamycin) indication? | Immune suppresion after kidney transplantation in combination with cyclosporine and corticosteroirds |
Sirolimus (rapamycin) Toxicity? | Hyperlipidemia, Thrombocytopenia, leukopenia |
Azathioprine MoA? | Antimetabolite precursor of 6-mercaptopurine that interferes with the metabolism and synthesis of nucleic acids. Toxic to proliferating lymphocytes |
Azathioprine CLINICAL USE | Kidney transplantation, autoim mune disorders (including glomeru lonephritis and hemolytic anemia) . |
Azathioprine Toxicity | Bone marrow suppression. Active metabol ite mercaptopurine is metabol ized by xanth ine oxidase ; thus, toxic effects may be increased by allopurinol. |
Muromonab-CD3 {OKT3) MoA | Monoclonal antibody that binds to CD3 (epsilon chain) on the surface of T cel l s . Blocks cellular i nteraction with C D 3 protein responsible for T-cel l signal transduction. |
Muromonab-CD3 {OKT3) Indication | I mmunosuppression after k idney transplantation |
Muromonab-CD3 {OKT3) toxicity | Cytokine release syndrome, hypersensitivity reaction |
Aldesleukin (interleukin-2 ) Indication | Renal cell carcinoma, metastatic melanoma |
Epoetin alfa (erythropoietin) Indication | Anem ias (especially in renal fai lure) |
Filgrastim (granulocyte colony-stimulating factor Indication | Recovery of bone m arrow |
Sargramostim (granulocyte-macrophage colonystimulating Indication factor) | Recovery of bone marrow |
a-interferon Indication | Hepatitis B and C, Kapos i 's sarcoma, leuke m ias, mal ignant melanoma |
beta-interferon Indication | Multiple sclerosis |
gamma interferon Indication | Chron ic granulomatous d isease |
Oprelvekin (IL-11) Indication | Thrombocytopen i a |
Thrombopoietin Indication | Thrombocytopenia |
Muromonab-CD3 | Prevent acute transplant rejection |
Digoxin I mmune Fab | Antidote for digoxin intoxication |
lnfliximab | Crohn's d i sease, rheumatoid arthritis, psoriatic arthritis, ankylosing spondyl itis |
Adalimumab | Crohn's d isease, rheumatoid arthritis, psoriatic arthritis |
Abciximab | Prevent card iac ischem i a in unstable angina and i n patients treated with percutaneous coronary intervention |
Trastuzumab | HER2-overexpressing breast cancer |
Rituximab | CD 20; B -cell non-Hodgkin's lymphoma |
O malizumab | IgE; Additional line of treatment for severe asthma |