Immunology - Part 1
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2017-05-18 14:46
Lymphoid structures
| Question | Answer |
|---|---|
| Follicle | Site of B-cell localization and proliferation - in outer cortex 1° follicle - dense and dormant 2° follicle - pale central germinal centers & active |
| Medulla | Has cords - closely packed lymphocytes and plasma cells Sinuses - reticular cells and macrophages |
| Paracortex | T cells Between follicles and medulla Becomes greatly enlarged during an extreme cellular immune response (viral) Not present in DiGeorge syndrome |
| Upper back, lateral breast drains to | axillary LN |
| Stomach drains to | Celiac LN |
| Duodenum, jejunum drains to | Superior mesenteric LN |
| Sigmoid colon drains to | Colic → inferior mesenteric LN |
| Rectum and anal canal (above pectinate line) drain to | Internal iliac LN |
| Anal canal (below pectinate line) drains to | Superficial inguinal LN |
| Testes drain to | Superficial & deep plexuses → para-aortic LN |
| Scrotum drains to | Superficial inguinal LN |
| Thigh (superficial) drains to | superficial inguinal |
| Lateral side of dorsum of foot drains to | popliteal |
| Right lymphatic duct | drains right arm, right chest, and right half of head |
| Thoracic duct | drains everything but the right arm, right chest, and right side of head |
Spleen and Thymus
| Question | Answer |
|---|---|
| Macrophages found where? | red pulp |
| T cells found where? | periarterial lymphatic sheath (PALS)- white pulp |
| B cells found where? | white pulp |
| Macrophages remove what? | encapsulated bacteria (Please SHiNE my SKiS) |
| How does splenic dysfunction ↑ susceptibility to encapsulated organisms? | ↓ IgM → ↓ complement activation → ↓ C3b opsonization → ↑ susceptibility to Please SHiNE my SKiS |
| What would you find postsplenectomy? | Howell-Jolly bodies (nuclear remnants) Target cells Thrombocytosis Lymphocytosis |
| Where do T-cells mature and differentiate? | Thymus |
| Where do B cell mature and differentiate? | Bone marrow |
| Embryo origination of thymus | epithelium of 3rd brachial pouches |
| Lymphocyte origin | mesenchymal |
| Cortex of thymus contains | immature T cells |
| Medulla of thymus contains | mature T cells epithelial reticular cells containing Hassall's corpuscles |
| Positive selection occurs where? | cortex (self MHC restriction) |
| Negative selection occurs where? | Medulla (non-reactive to self) |
Lymphocytes
| Question | Answer |
|---|---|
| Cells of the innate immunity | neutrophils, macrophages, dendritic cells, natural killer cells (lymphoid origin) and complement |
| Cells of the adaptive immunity | T cells, B cells, and circulating antibody |
| MHC stands for what and is encoded by what? | major histocompatibility complex Encoded by human leukocyte antigen (HLA) genes |
| MHC I (made up of what, does what, and expressed where) | HLA-A, HLA-B, HLA-C Binds TCR and CD8 Expressed on all nucleated cells (not RBCs) |
| MHC I antigen processing | Antigen is loaded in RER with mostly intracellular peptides Mediates viral immunity Pairs with B2-microglobulin which aids in transport to cell surface |
| MHC II (made up of what, does what, and expressed where?) | HLA-DR, HLA-DP, HLA-DQ Binds TCR and CD4 Expressed only on antigen-presenting cells (APCs) |
| MHC II antigen processing | Antigen is loaded following release of invariant chain in an acidified endosome |
HLA assoc'd diseases
| Question | Answer |
|---|---|
| A3 HLA subtype assoc with what? | Hemochromatosis |
| B27 HLA subtype assoc with what? | PAIR Psoriasis, Ankylosing spondylitis, Inflammatory bowel disease, Reiter's syndrome |
| DQ2/DQ8 HLA subtype assoc with what? | Celiac disease |
| DR2 HLA subtype assoc with what? | MS, hay fever, SLE, Goodpasture's |
| DR3 HLA subtype assoc with what? | Diabetes mellitus type 1, Graves' disease |
| DR4 HLA subtype assoc with what? | Rhematoid arthritis, DM type 1 |
| DR5 HLA subtype assoc with what? | Pernicious anemia → B12 def., Hashimoto's thyroiditis |
| NK cells do what | Use perforin and granzymes to induce apoptosis of virally infected cells and tumor cells Kill when there is a nonspecific activation signal on target cell or an absence of class 1 MHC on target cell surface They are the only lymphocyte member of the innate immune system |
| NK cells' activity is enhanced by | IL-2, IL-12, IFN-B, and IFN-a |
B cells and T cells
| Question | Answer |
|---|---|
| Major fn of B cells | Make antibody → opsonize bacteria, neutralize viruses (IgG) Active complement (IgM, IgG) Sensitize mast cells (IgE) Hyperacute and humorrally mediated acute/chronic organ rejection |
| Type 1 hypersensitivity | Allergy IgE |
| Type 2 hypersensitivity | Cytotoxic IgG |
| Type 3 hypersensitivity | Immune complex IgG |
| Major fn of T cells | CD4+ - help B cells make antibody and produce cytokines to activate other immune cells CD8+ kill virus-infected cells directly Acute/chronic cellular organ rejection |
| Type 4 hypersensitivity | T-cells! - Delayed cell-mediated hypersensitivity |
| CD8+ T cell becomes what? | Cytotoxic T cell In LN |
| CD4+ T cell becomes what? | Helper t-cell → Th1 cell and Th2 cell In LN |
| Positive selection | Thymic cortex T cells expressing TCRs capable of binding surface self MHC molecules survive |
| Negative selection | Thymic medulla T cells expressing TCRs with high affinity for self anitgens undergo apoptosis |
| Antigen presenting cells | Dendritic cell - only APC that can activate naive T-cell Macrophage B cell 2 signals are required for Tcell/Bcell activation and class switching |
| Naive T cell activation (4 steps) | 1. Foreign body is phagocytosed by dendritic cell 2. Foreign antigen is presented: - on MHC II and recognized by TCR on Th (helper) cell - on MHC I to Tc (cytotoxic) cells 3. Costimulatory signal is given by interaction of B7 and CD28 4. Th cell activates/produces cytokines Tc cell activates and is able to recognize/kill virus-infected cells |
| B cell activation and class switching (4 steps) | Helper T cell activation (Th cell) 2. B cell receptor-mediated endocytosis - antigen is presented on MHC II from B cell and recognized by TCR on Th cell 3. CD40 on B cell binds to CD40 ligand on Th cell 4. Th cell secretes cytokines → determines Ig class switching of B cell - B cell activates and undergoes class switching, affinity maturation and antibody production |
| Th1 helper T cell secretes what and activates what? | IFN-gamma Activates macrophages |
| Th2 helper T cell secretes what and activates what? | IL-4,5,10,13 Recruits eosinophils for parasite defense and promostes IgE production by B cells |
| Th1/Th2 - what inhibits what? | Th1 inhibits Th2 with IFN-gamma Th2 inhibits Th1 with IL-4 and IL-10 |
| Macrophage/lymphocyte interaction | Lymphs activate macs with IFN-gamma Macs activate lymphs with IL-1 & TNF-a |
| Cytotoxic T cells | Kill virus-infected, neoplastic, and donor graft cells by inducing apoptosis Release cytotoxic granules containing preformed proteins Have CD8 which binds to MHC 1 on virus-infected cells |
| Contents of granules of cytotoxic T cells | Perforin - helps deliver the content of granules into target cell Granzyme - a serine protease, activates apoptosis inside target cell Granulysin - antimicrobial, induces apoptosis |
| Regulatory T cells fn | Help maintain specific immune tolerance by suppressing CD4 and CD8 T-cell effector functions Produce anti-inflammatory cytokines: IL-10, TGF-B |
| Regulatory T cells express what? | CD3,4,25 (alpha chain of IL-2 receptor) |
Antibody structure and function
| Question | Answer |
|---|---|
| Variable part of L and H chains do what? | recognize antigens |
| Fc portion of IgM and IgG does what? | fixes complement |
| Heavy chain does what? | contributes to Fc and Fab fractions |
| Light chain does what? | contributes only to Fab fraction |
| Fab | Antigen-Binding fragment Determines idiotype: only 1 antigenic specificity expressed per B cell |
| Fc | Constant Carboxy terminal Complement binding at CH2 (IgG + IgM only) Carbohydrate side chains Determines idiotype (IgM, IgD, etc) |
| Antibody diversity is generated by | - Random recombination of VJ (light chain) or V(D)J (heavy chain) genes - Random combination of heavy chains with light chains Somatic hypermutation (following antigen stimulation) Addition of nucleotides to DNA during recombination by terminal deoxynucleotidyl transferase |
| General purpose of antibody | Promotes opsonization Prevents bacterial adherence Activates complement, enhancing opsonization and lysis |
Immunoglobulin isotypes
| Question | Answer |
|---|---|
| Mature B lymphocytes express what? | IgM and IgD |
| Isotype switching involves what? | Gene rearrangement - mediated by cytokines and CD40 ligand |
| IgG | Main antibody in 2° (delayed) response to an antigen - most abundant isotype Fixes complement Crosses placenta - provides passive immunity to infants Opsonizes bacteria Neutralizes bacterial toxins and viruses |
| IgA | Prevents 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 early breast milk (colostrum) Transported by epithelial cells by transcytosis - picks up secretory component |
| IgM | Produced in the 1° (immediate) response to an antigen Fixes complement but does not cross the placenta Antigen receptor on the surface of B cells Shape of pentamer (on B cells) traps free antigens out of tissue while humoral response evolves |
| IgD | Found on the surface of many B cells in the serum - unclear function |
| IgE | Binds mast cells and basophils cross-links when exposed to allergen → mediating immediate (type 1) hypersensitivity via histamine Activates eosinophils to fight worms Lowest concentration in serum |
| Thymus-independent antigens | Antigens like LPS or polysaccharide capsular antigens that don't have a peptide component → stimulate release of antibodies without producing immunologic memory |
| Thymus-dependent antigens | Contain a protein component (diphtheria vaccine) Class switching and memory occurs thanks to contact of B cells with Th cells (CD40-CD40) |
Complement
| Question | Answer |
|---|---|
| Activation | Classic pathway - IgG or IgM mediated Alternate pthwy - microbe surface molecules Lectin pthwy - mannose or other sugars on microbe surface |
| C3b fn | opsonization |
| C3a, C5a fn | anaphylaxis |
| C5a fn | neutrophil chemotaxis |
| C5b-9 fn | cytolysis by MAC |
| MAC defends what? | gram-negative bacteria |
| Opsonins | C3b and IgG - 1° C3b also helps clear immune complexes |
| Inhibitors | Decay-accelerating factor C1 esterase inhibitor prevents complement activation on self cells (RBCs) |
| C1 esterase inhibitor deficiency | → hereditary angioedema ACE inhibitors are contraindicated |
| C3 deficiency | → severe, recurrent pyogenic sinus and respiratory tract infections ↑ susceptibility to type III hypersensitivity reactions |
| C5-C9 deficiencies | → recurrent Neisseria bacteremia |
| DAF (GPI anchored enzyme) deficiency | → complement-mediated lysis of RBC's and paroxysmal nocturnal hemoglobinuria (PNH) |
Cytokines
| Question | Answer | Column 3 |
|---|---|---|
| IL-1 | Fever & acute inflammation Adhesion molecules on endothelium Chemokine secretion → recruits leukocytes | secreted by macrophages |
| IL-2 | stimulates T cells, helper, cytotoxic, and regulatory | secreted by all T cells |
| IL-3 | stimulates bone marrow growth and differentiation Functions like GM-CSF | secreted by all T cells |
| IL-4 | stimulates IgE production (and IgG) Induces differentiation into Th2 cells B-cell growth | secreted by Th2 cells |
| IL-5 | stimulates IgA production B cell growth eosinophils growth and differentiation | secreted by Th2 cells |
| IL-6 | Fever & acute-phase proteins | Secreted by macrophages and Th2 cells |
| IL-8 | Major chemotactic factor for neutrophils Cleanup on aisle 8! | Secreted by macrophages |
| IL-12 | Induces differentiation of T cells into Th1 cells Activates NK cells | Secreted by macrophages and B cells |
| TNF-a | Mediates septic shock Activates endothelium Leukocyte recruitment, vascular leak | secreted by macrophages |
| Interferon-gamma | Activates macrophages and Th1 cells → ↑ MHC I and II expression in all cells Suppresses Th2 cells Antiviral and antitumor properties | secreted by Th1 cells |
| Cytokines from macrophages | IL1,6,8,12, TNF-a | |
| Cytokines from all T cells | IL-2,3 | |
| Cytokines from Th1 cells | IFN-γ | |
| Cytokines from Th2 cells | IL-4,5,6,10 | |
| IFN-α & β | inhibit viral protein synthesis via prodction of ribonuclease | |
| IL-10 | Modulates inflamatory response Inhibits actions of activated T cells and Th1 Fn's similar to TGF-β | Th2 cells and regulatory T cells |
Cell surface proteins
| Question | Answer |
|---|---|
| T cells | TCR CD3 CD28 |
| Helper T cells | CD4 CD40 ligand |
| Cytotoxic T cells | CD8 |
| B cells | Ig CD19 CD20 CD21 CD40 MHC II, B7 |
| Macrophages | CD14 CD40 MHC II, B7 Fc and C3b receptors (enhanced phagocytosis) |
| NK cells | CD16 CD56 |
| TCR | binds antigen-MHC complex |
| CD3 | assoc w TCR for signal transduction |
| CD28 | binds B7 on APC |
| Ig | binds antigen |
| CD21 | receptor for EBV |
| Fc and C3b receptors | enhanced phagocytosis |
| Cd16 | Binds Fc of IgG |
| CD56 | unique marker for NK |
Random
| Question | Answer |
|---|---|
| Action of superantigens | Strep pyogenes & Staph aureus cross-link the B region of the T-cell receptor to the MHC class II on APCs → can activate any T cell → massive release of cytokines |
| Endotoxins/LPS action | Gram-negative bacteria Bind CD14 → directly stimulating macrophages Th cells are not involved |
| Antigen variation - classic bacterial examples | Salmonella - 2 flagellar variants Borrelia - replasing fever Neisseria gonorrhoeae - pilus protein |
| Antigen variation - virus | influenza: major=shift - minor=drift |
| Antigen variation - classic parasite example | trypanosomes - programmed rearrangement |
| When to give passive immunity after exposure | Tetanus toxin Botulinum toxin HBV Rabies virus |
| Live attenuated vaccine mechanism | Pathogen loses pathogenicity but still grows in host Cellular response - life-long immunity but could revert to virulent form |
| Live attenuated vaccine examples | Measles mumps polio (sabin) rubella varicella yellow fever |
| Inactivated (killed) vaccine mechanism | Pathogen is inactivated but maintains epitope structure on surface antigens Humoral immunity - stable/safer, but requires booster shots |
| Inactivated (killed) vaccine examples | Cholera Hep A Polio (salk) Rabies |
