Step 1 - Immuno 1

denniskwinn's version from 2015-04-25 16:03


Question Answer
Lymph Node Functionsnonspecific filtration by macrophages, storage and activation of Band T cells, antibody production
FolliclesSite of B-cell localization and proliferation. In outer cortex. primary follicles are dense and dormant. Secondary follicles have pale central germinal centers and are active.
MedullaConsists of medullary cords (closely packed lymphocytes and plasma cells) and medullary sinuses. Subcapsular sinus, Medullary sinuses communicate with efferent lymphatic lymphatics and contain reticular cells and macrophages.
ParacortexHouses T cells. Region of cortex between follicles and medulla. Contains high endothelial venules through which T and B cells enter from blood. In an extreme cellular immune response, paracortex becomes greatly enlarged(response to virus) Not well developed in patients with DiGeorge syndrome.
Upper limb, lateral breast primary LN drainage siteAxillary
Stomach primary LN drainage siteCeliac
Duodenum, Jejunumprimary LN drainage siteSuperior mesenteric
Sigmoid colon primary LN drainage siteColic→Inferior mesenteric
Rectum (lower part), anal canal above pectinate line primary LN drainage siteInternal iliac
Anal canal below pectinate line primary LN drainage siteSuperficial iguinal
Testes primary LN drainage siteSuperficial and deep plexuses→ para-aortic
Scrotum primary LN drainage sitesuperficial inguinal
Thigh (s uperficial) primary LN drainage sitesuperficial inguinal
Lateral side of dorsum of foot primary LN drainage sitePopliteal
Right lymphatic ductdrains right arm and right half of head
Thoracic ductdrains everything else
Spleen sinusiodsLong, vascular channel in red pulp with fenestrated "barrel hoop" basement membrane. Macrophages found nearby.
T cells in the spleenfound in the periarterial lymphatic sheath (PALS) and in white pulp of the spleen .
B cells in the spleenfound in follicles within the white pulp of the spleen
Splenic dysfunction↓ IgM→ ↓ complement activation→↓ C3b opsonization→↑ susceptibility to encapsulated organisms (S. pneumoniae, H. influenzae, Salmonella,N. meningitidis).
PostsplenectomyHowell-Jolly bodies (nuclear remnatns), Target cells, Thrombocytosis
Thymus1. Site ofT-ceil differentiation and maturation. 2. Encapsulated. From epithelium of 3rd branchial pouches. 3. Lymphocytes of mesenchymal origin. 4. Cortex is dense with immature T cells; medulla is pale with mature T cells and epithelial reticular cells and contains Hassall's corpuscles. 5. Positive (MHC restriction) and negative selection 6. (nonreactive to self) occur at the corticomedullary junction.


Question Answer
Innate immunityreceptors that recognize pathogens are germline encoded. Response to pathogens is fast and nonspecific. No memory. Consistes of neutrophils, macrophages, dendritic cells, natural killer cells and complement
Adaptive immunityreceptors that recognize pathogens undergo V(D)J recombination during lymphocyte development. Response is slow on first exposure, but memory response is faster and more robust. Consists of T cells, B cells and circulating antibody.
T cell differentiationt-cell precursor in bone marrow, CD4 and 8+ T cell in cortex (positive selection) then negative selection in the medulla.
Cytotoxic T cellsCD8+, kills virus-infected neoplastic and donor graft cells
Th1 cellsCell mediated response - Makes IL-2, IFN gamma, and activates macrophages and CD8+ T cells . . Inhibited by IL-10
Th2 cellsHumoral response - Make IL-4, IL-5, IL-10 and help B cells make antibody (lgE > IgG); inhibited by IFN-gamma
MHC = major histocompatibility complex, encoded by Human Leukocyte Antigen (I-ILA) genes; present antigen fragments to T cells and bind TCR.
MHC 1= HLA-A, HLA-B, HLA-G, Expressed on almost all nucleated cells. Antigen is loaded in RER of mostly intracellular peptides. Mediates viral immunity. Pairs with Beta 2 microglobulin (aids in transport to cell surface).
MHC II = HLA-DR, HLA-DP, HLA-DQ. Expressed only on antigen-prescnting cells (APCs), Antigen is loaded following release of invariant chain in an acidified endosome
HLA A3 associated diseasesHemochromatosis
HLA B27 associated diseasesPAIR - Psoriasis, Ankylosing spondylitis, IBD, Reiter’s
HLA B8 associated diseases Grave’s disease
HLA DR2 associated diseases MS, Hay fever, SLE, goodpastures
HLA DR3 associated diseasesDM I
HLA DR4 associated diseases RA, DM I
HLA DR5 associated diseasesPernicious anemia→ B12 deficiency, hashimoto’s thyroiditis
HLA DR7 associated diseasesSteroid-responsive nephrotic syndrome
Major B cell functions (5)1. Make antibodies 2. IgG antibodies opsonize bacteria, neutralize viruses 3. Allergy (type I hypersentivity, IgE) 4. Cytotoxic (type II) and immune complex hypersentivity (IgG) 5. Antibodies cause organ rejection (hyperacute)
Major T cell function (4)1. Cd4+ T cells help B cells make antibody and produce gamma interferon, which activates macrophages 2. Kill virus infected cells directly (CD8+ T cells) 3. Delayed cell mediated hypersensitivity (type IV) 4. Organ (allograft) rejection (acute and chronic)
Natural killer cells1. Use perforin and granzymes to induce apoptosis of virally infected cells and tumor cells. 2. Only lymphocyte member of innate immune system. 3. Activity enhanced by IL-12, IFN-beta, and IFN-alpha.. Induced to kill when exposed to a nonspecific activation signal on target cell and/or to an absence of class I MHC on target cell surface.


Question Answer
Cd3 complexcluster of polypeptides associated with a T-cell receptor. Important in Signal transduction
Antigen presenting cellsMacrophages, B cells, Dendritic cells
Macrophage - lymphocyte interactionActivated lymphocytes realease IFN gamma and macrophages release IL-1 and TNF alpha and they stimulate one another
Superantigen effects on immune systemfrom s. Pyogenes and s.aureus cross link beta region of T cell receptor to the MHC class II on APCs. Results in unccoordinated release of IFN gamma from TH1 cells and subsequent release of IL1, IL6 and TNF alpha from macrophages
Endotoxin effects on immune systemfrom gram - bacteria - directly stimulate macrophages by binding to CD14 (endotoxin receptor) - Th cells are not involved.
Th activation1. Foreign body is phagocytosed by APC 2. Foreign antigen is presentcd on MHC II and recognized by TCR on Th cell (signal 1) 3. "Costimulatory signal" is given by interaction of B7 and CD28 (signal 2)4. Th cell activated to produce cytokines
Tc activation 1. Endogenously synthesized (viral or self) proteins are presented on MHC I and recognjzed by TCR on Tc cell (signal 1) 2. IL-2 from Th cell activates Tc cell to kill virus-infected cell (signal 2)
B-cell class switching1. IL-4, IL-5 , or IL-6 from Th2 cell (signal 1) 2. CD40 receptor activation by binding CD40 ligand on Th cell (signal 2)
Antibody structure and functionVariable part of L and H Chains recognizes antigens Fc portion of IgM and lgG fixes complement. Hcavy chain contributes to Fc and Fab fractions. Light chain contributes only to Fab fraction
FabAntibody part - Antigen-binding fragment, Determines idiotype: unique antigen-binding pocket; only 1 antigenic specificity expressed per B cell
FcAntibody part - Constant, Carboxyl terminal, Component binding at CH2 (IgG+IgM only), Carbohydrate side chains, Determines isotype (IgM, IgD, etc)
Antibody diversitygenerated by 1. Random “recombination” of VJ (light-chain) or V(D)J (heavy chain) genes 2. Random combination of heavy chains with light chains 3. Somatic hypermutation (following antigen stimulation) 4. Addition of nucleotides to DNA during “recombination” by terminal deoxynucleotidyl transferase
Mature B lymphocytes expressIgM and IgD on their surfaces - they may differentiate by isotypes switching (alternative splicing of mRNA; mediated by cytokines and CD40 ligand) into plasma cells that secrete IgA, IgE or IgG


Question Answer
IgGMain antibody in secondary (delayed) response to an antigen. Most abundant isotype in blood. Fixes complements, crosses the placenta (provides infants with passive immunity) - opsonizes bacteria, neutralizes bacterial toxins and viruses
IgAPrevents attachment of bacteria and viruses to mucous membranes; does not fix complement Monomer (in circulation) or dimer (when secreted). Found In secretions (tears, saliva, mucus) and breast milk (known as "colostrum ") Picks up secretory component from epithelial cells before secretion.
IgMProduced in the primary (immediate) response to an antigen. Fixes complement but does not cross the placenta Antigen receptor on the surface of B cells. Monomer on B cell or pentamer. Shape of pentamer allows it to efficiently trap free antigens out of tissue while humoral response evolves.
IgDUnclear function. Found on the surface of many B cells in serum.
IgEBinds mast cells and basophils; cross-links when exposed to allergen, mediating immediate (type I) hypersensitivity through release of inflammatory mediators such as histamine. Mediates immunity to worms by activating eosinophils. Lowest concentration in serum.
Allotype (polymorphism)Ig epitope that differs among members of same species. Can be on light chain or heavy chain (represent different allelles)
IsotypeIg epitope common to a single class of Ig (5 classes determined by heavy chain)
Idiotype (specific for a given antigen)Ig epitope determined by antigen-binding sites - hypervariable region is unique
Thymus independent antigensantigens lacking a peptide component; cannot be presented by MHC to T cells (e.g.LPS) - stimulates release of IgM antibodies only and do not result in immunologic memory
Thymus-dependent antigensantigens containing a protein component - class switching and immunologic memory occur as a result of direct contact of B cells with Th cells (CD40-CD40 ligand interaction) and release of IL-4, IL-5 and IL-6.
IL-11. Secreted by macrophages 2. Causes acute inflammation. 3. Induces chemokine production to recruit leukocytes, activates endothelium to express adhesion molecules. An endogenous pyrogen
Cytokine mnenomicHot T-Bone stEAk - IL-1: fever(hot), IL-2: stimulates T cells, IL-3: stimulates Bone marrow, IL-4: stimulates IgE production, IL-5: stimulates IgA production
IL-2Secreted by Th cells - stimulates growth of helper and cytotoxic T cells
IL-3Secreted by activated T cells. Supports the growth and differentiation of bone marrow stem cells. Has a function similar to GM-CSF
IL-4Secreted by Th2 cells. Promotes growth of B cells - enhances class switching to IgE and IgG
IL-5Secreted by Th2 cells. Promotes differentiation of B cells. Enhances class switching to IgA. Stimulates production and activation of eosinophils.
IL-6Secreted by Th cells and macrophages. Stimulates production of acute-phase reactants and immunoglobulins
IL-8Secreted by macrophages - major chemotactic factor for neutrophils
IL-10Secreted by regulatory T cells, inhibits actions of activated T cells. Activates Th2, inhibits Th1
IL-12Secreted by B cells and macrophages. Activates NK and TH1 cells
Gamma interferonsecreted by TH1 cells, stimulates macrophages, activates Th1, inhibit Th2
TNFSecreted by macrophages. Mediates septic shock. Causes leukocyte recruitment, vascular leak.
Helper T cell Cell surface proteinsCD4, TCR, CD3, CD28, CD40L
Cytotoxic T cells Cell surface proteinsCD8, TCR, CD3
B cells Cell surface proteinsIgM, CD19, CD20, CD21 (receptor for EBV), CD40, MHC II, B7
Macrophage Cell surface proteinsMHC II, B7, CD40, CD14, Receptors for Fc and C3b
NK Cell surface proteinsReceptors for MHC I, CD16 (binds Fc of IgG), CD56
Cell surface proteins on all cellsMHC I
Primary opsonins in immune systemC3b and IgG -
Why no self complementDAF (decay-accelerating factor) and Cl esterase inhibitor help prevent complement activation on self-cells
C3bopsonization, Binds Bactcria.
C3a , C5a Anaphylaxis.
C5aneutrophi; chemotaxis.
C5b-9cytolysis by membrane attack complex (MAC)
Deficiency of Cl esterase inhibitor leads to hereditary angioedema.
Deficiency of C3leads to severe, recurrent pyogenic sinus and respiratory tract infections; ↑ susceptibility to type III hypersensitivity reactions.
Deficiency of C 5- C8 leads to Neisseria bacteremia.
Deficiency of DAF (GPI anchored enzyme) leads to complement-mediated lysis of RBCs and paroxysmal nocturnal hemoglobinuria (PNH).
Draw complement pathwaydraw
Interferon mechanismproteins that place uninfected cells in an antiviral state. Induce the production of a ribonuclease that inhibits viral protein synthesis by degrading viral mRNA (but no host mRNA)
Interferons Alpha and Betainhibit viral protein synthesis
Gamma interferon↑ MHC I and II expression and antigen presentation in all cells, Activates NK cells to kill virus- infected cells
Active immunityInduccd after exposurc to foreign antigens. Slow onset. Long-lasting protection (memory)
Passive immunityBased on receiving preformed antibodies from another host. Rapid onset. Short life span of antibodies (half-life = 3 weeks) Example: IgA in breast milk
Things to passive immunizeTetanus toxin, Botulinum toxin, HBV or Rabies virus - give preformed antibodies (Passive)
AnergySelf-reactive T cells become non-reactive without costimulatory molecule, B cells also become anergic but tolerance less complete than in T cells
Granulomatous diseases1. Tuberculosis, 2. Fungal infections (e.g., histoplasmosis) 3. Syphilis 4. Leprosy 5. Cat scratch fever, 6. Sarcoidosis, 7. Crohn's disease, 8. Berylliosis
Mechanism of granuloma formationAPC takes in pathogen, activate Th cell which produces IL-2 and IFN gamma which differentiates moncytes to macrophages to epitheliod cells and giant cells which are components of granuloma along with fibroblasts and lymphocytes