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76 Cards in this Set
- Front
- Back
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Three ways complement is activated
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Classical - IgG bound to Ag on microbial surface
Alternative - triggered directly by bacterial cell surfaces Lectin - mannin-binding lectin binds to carbs on microbe surface |
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Classical complement pathway (quick run through order of pathway)
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IgG binds to Ag on microbe surface
Order of binding: C1q binds Fc -> C1r+C1s Activated C1 cleaves C4 C14b cleaves C2 -> C14b2b cleaves C3 -> C14b2b3b cleaves C5 C5b binds C6,7,8,9 to form MAC (1 4 2 3 5 6 7 8 9) |
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Membrane attack complex
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C5b + 6 + 7 + 8 + 9
poly C9 forms pore in microbe Fluids rush in causing cell swelling/lysis |
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Four functions of complement
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1) opsonization: IgG + C3 coats microbe causing phagocytosis by neutrophils and macrophages
2) chemotaxis - C3a and C5a attract phagocytic cells to site 3) anaphylatoxins - C3a and C5a degranulate mast and basophils to cause local inflammation 4) lysis of organisms coated w/ specific antibody by C8 and C9 |
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Inhibitory regulation of complement
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C1 inhibitor (C1-INH) turns off complement by causing C1r+s to dissociate from complex
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Alternative complement pathway (and inhibition)
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Activated by specific bacterial and viral products like LPS
C3b is always present due to natural breakdown of C3 -> C3b + factors B+D and properdin form C3 convertase C3bBbP that splits C3 in C3a and b to continue classical pathway at cleaving C5 Factors H+I inhibit C3bBbP |
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Lectin-binding complement pathway
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Activated by organisms with mannose on surface
Mannose binding lectin (MBL) -> MASP1 -> MASP2 -> C4b2b -> C3 cleavage -> classical complement pathway |
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Lupus and complement deficiencies
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Absence of C1q, C2, or C4
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Hereditary angioedema
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Localized edema of skin and mucosa
Swelling in face and limbs Deficiency of C1-INH |
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Regulation by CTLA-4
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Present on T cell and competes for B7 on APC
Early in response B7 interacts w/ CD28 and late with CTLA-4 to suppress response |
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Regulation by Tregs
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Inhibitory T cells that make IL-10 and TGFbeta to suppress T cells
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Activation induced cell death
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Normal T cells have FasL
Late in response activated T cells express Fas Fas+FasL -> apoptosis |
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Cytokine-mediated regulation of T cells
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APC makes IL-10 and TGFβ that inhibit
TH1 makes IFNγ to inhibit TH2 TH2 makes IL-4 to inhibit TH1 |
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Define immunologic tolerance
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Lack of response to specific antigen
Failure to induce specific immunity to that antigen |
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Central tolerance vs peripheral tolerance
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Central - developed in thymus
Peripheral - outside thymus: clonal deletion, clonal anergy, fetal tolerance |
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Clonal deletion
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Continuous exposure to self antigens leads to T cell apoptosis via Fas
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Clonal anergy
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Absence of costimulators leads to too little response
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6 Immunological factors for autoimmunity
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1. Exposure of hidden antigens - eg due to tissue damage
2. Polyclonal lymphocyte activation - eg EBV stimulates B cells 3. Excessive cytokine production upregulates adhesion molecules and costimulators 4. Defective Fas and FasL interaction inhibits apoptosis 5. Defective Tregs 6. Imbalance of CTLA-4 and CD28 doesn't turn down immune response |
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Superantigens and autoimmunity (eg)
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Superantigens stimulate T cells by attaching to outside of TCR+ MHC II
eg staphylococcal food poisoning where toxin superantigen is made -> toxic shock syndrome |
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4 Microbial factors in autoimmunity
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1. Molecular mimicry - eg rheumatoid fever, Ag shares cross reactivity w/ self Ag
2. Microbes damage tissue and release hidden Ag 3. Direct activation of lymphocytes inappropriately 4. Function as adjuvants to stimulate response |
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Syngeneic graft
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Between genetically identical people
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Two ways grafts are recognized by T cells
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1. Recipient T cells recognize donor MHC peptides presented by recipient APCs (normal)
2. Recipient T cell recognize unprocessed donor MHC molecules on graft APC (unusual) |
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Hyperacute rejection
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Within minutes/hours
Due to preformed Ab in recipient against donor |
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Acute rejection
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10-14 days
Due to cell-mediated immunity and some Ab |
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Chronic rejection
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Months or years
Due to T cells, Ab, NK cells |
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Effector mechanisms in graft rejection (4)
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1. Direct contact w/ CD8 cells
2. cytokine release -> inflammation and macrophage activation 3. Ab against donor HLA -> complement + ADCC 4. NK cell attack |
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Graft versus host disease (3 requisites)
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Donor CD4 T cells against host MHC w/ host antigens produces cytokine storm and inflammation
Requires: Graft contains live T cells Recipient is immunosuppressed Donor and recipient have different HLA |
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Cyclosporine and FK506
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Immunosuppressors that inhibit T cell phosphatase thereby inhibiting cytokine production
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Corticosteroids as drugs in transplantation
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Inhibit cytokines
Anti inflammatory |
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Anti-CD3 and anti IL-2
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Immunosuppressors in transplantation
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Types of antigens on tumor cells (4)
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1. Virally controlled antigens in tumors produced by viruses (EBV)
2. Expression of altered genes - oncofetal protein, mutant/abnormal proteins, tissue specific Ag 3. Lack MHC I so T cells can't kill (NK can) 4. Tissue specifc Ag (PSA, B/T cell markers) |
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Natural Killer Cells (activated by?, functions (3))
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Activated by IL-2, IL-12, IFNγ
Destroy infected and malignant cells lacking MHC I Have Fc receptors to bind Ig -> ADCC Produce cytokines |
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What is the principle immune reaction to kill tumor cells?
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Cytotoxic CD8 using granzymes + perforin, production of TNF, and expression of FasL
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How do tumors escape immune response? (3)
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1. Release immunosuppressive factors like IL-10 and TGFβ
2. Release factors to activate Tregs 3. Select antigen-negative variants |
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Hypersensitivity
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Too much immune response causing damage
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Immediate hypersensitivity (Type I) (eg)
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Allergy
IgE mediated causing mast cell and basophil degranulation Bronchial asthma, allergic rhinitis |
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Immediate hypersensitivity mechanism
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Ag is administered to skin or mucus membrane -> favors IgE
APC activate TH2 -> IL-2 + IL-2R -> proliferation -> IL-4 -> IgE |
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Immediate hypersensitivity sensitization (5 steps)
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First exposure
APC present allergen to TH1/2 cells Production of IL-4 Stimulate B cells to make IgE Mast cells and basophils are primed to bind allergen w/ IgE |
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Immediate hypersensitivity early phase mediators (4)
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Histamine - inflammation
Proteases - tissue degradation Leukotrienes - pro inflammatory Platelet activating factor - massive vasodilation and bronchoconstriction |
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Immediate hypersensitivity late phase (when?)
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5-6 hours
Cytokines released from cells that have moved in: T cells, macrophages, eosinophils |
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Treatment for late phase type I allergic reactions
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Corticosteroids to stop cytokine production
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Treatments for type I allergic reactions (3)
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Epinephrine for anaphylactic shock
Omalizumab inhibits IgE binding to mast cells Hyposensitization therapy - shots to progressively raise IgG and lower IgE |
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Mechanisms other than IgE that can degranulate mast cells (6)
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C5a and C3a
Heat, cold Pressure Exercise CNS effects via vagus nerve Direct effect of drugs on mast cells |
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Cytotoxic (type II) hypersensitivity
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Abnormal IgM or IgG Ab made against tissue
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Cytotoxic hypersensitivity (type II) mechanisms (3)
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Complement binds to Ab -> lysis
Ab recruits NK cells (ADCC) Ab recruits neutrophils for phagocytosis |
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Cytotoxic hypersensitivity (type II) examples (4)
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Autoimmune hemolytic anemia - Ab against RBC
Autoimmune thrombocytopenia - Ab against platelet Goodpasture's syndrome - Ab against glomerular BM Hyperacute graft rejection -Ab against graft |
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Myasthenia gravis (mechanisms and symptom)
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Type II
Ab against Ach receptors at neuromuscular junctions Causes internalization and degradation of Ach receptors Severe muscle weakness |
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Graves' disease (which type hypersensitivity?)
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Type II
Ab against thyroid stimulating hormone receptor Agonizes: TSH stimulates release of thyroid hormone, but is negatively regulated by thyroid hormone Ab interferes w/ negative regulation causing continual release and hyperthyroidism |
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Immune complex (type III) hypersensitivity
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Ag-Ab complexes are trapped in small blood vessels
Binding of complement triggers inflammatory reaction in joints, skin, kidney |
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Immune complex (type III) hypersensitivity mechanism
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Immune complexes bind complement
C3a and C5a (anaphylatoxins) induce degranulation of lysosomal enzymes Damages vessel wall (vasculitis) |
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Immune complex (type III) hypersensitivity examples (4)
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SLE - Ag-nuclear Ab complexes
Post-streptococcal glomerulonephritis - Anti-strep Ab -strep Ag trapped in glomeruli Serum sickness - Ag against foreign serum Drug reactions |
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Arthus reaction
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Localized immune complex disease
When Ag is introduced in individual who already has Ab Immune complexes at site attract neutrophils -> inflammation Eg observed in skin at site of allergy or tetanus booster shot |
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Farmer's lung
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Repeated exposure to moldy causes high levels of circulating IgG to spores in hay
Leads to Arthus reaction in lungs T cell infiltration leads to delayed hypersensitivity reaction |
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Delayed hypersensitivity
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Exactly like cell-mediated immunity but resulting in tissue damage
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DTH sensitization phase
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Like Ab-mediated hypersensitivity, sensitization is required
APC process antigen and present to TH1 resulting in proliferation that can produce DTH reaction on re-exposure |
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DTH effector phase (4)
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Like CMI
1. Cytokine production: IL-2, IFNγ 2. Endothelial cell activation 3. Macrophage activation via IFNγ 4. CD8 killing |
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Contact dermatitis and patch test
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DTH
Requires re-exposure Patch test - solution of suspected Ag is spread on skin. Look for area of induration and erythema to implicate sensitivity |
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Tuberculin skin test (Mantoux reaction) (what type hypersensitivity?)
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DTH Type IV
Inject PPD (purified protein derivative) of tuberculosis into skin If already had vaccine (BCG), test is always positive |
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Cell-mediated immunity is crucial in protecting against which four infectious agents?
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Intracellular bacteria (TB)
Large viruses (Pox, Herpes) Fungi (Candida albicans) Parasites (Toxoplasma) |
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General features of T cell deficiency (4)
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Reduced T cell zones in lymphoid organs
Reduced DTH reactions to common antigens Defective T cell responses to mitogens Intracellular infections |
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General features of B cell deficiency (3)
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Absent or reduced follicles and germinal centers
Reduced serum Ig Pyogenic bacterial infections |
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Neutrophil functions (3)
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Chemotaxis
Phagocytosis Killing |
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Neutrophil defects (3)
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Neutropenia - inadequate neutrophils (chemotherapy)
Defective opsonization (Ig or C3b deficiency) Defective killing |
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Chronic granulomatous disease (CGD) (4)
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X-linked
Neutrophils phagocytose but can't kill Inability to generate superoxide anion (killing granule) Granuloma - accumulation of cells around a central area, full of neutrophils |
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Leukocyte adhesion deficiency (LFA-1 deficiency) (2)
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LFA-1 makes vessels sticky
Failure to heal wounds |
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Chediak-Higashi syndrome (2)
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Giant lysosomal granules making neutrophils defective
Lethal from recurrent infections |
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X-linked (Bruton's) Agammaglobulinemia (3 and treatment)
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Absent IgA, IgM, IgG
pre-B cells, but no mature B cells in blood or germinal centers Mutation in Bruton's tyrosine kinase Treat w/ IVIG |
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IgA deficiency
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Common 1:700
With associated IgG2 or 4 -> respiratory and GI infections |
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Hyper IgM syndrome
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Mutation on CD40 L on T cell (necessary to interact w/ CD40 on B cell to promote class switching)
Recurrent infections, no germinal center |
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Common variable immunodeficiency (2, treatment)
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Low serum level of all Ig
Increased susceptibility to all infections Treat w/ IVIG |
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DiGeorge syndrome
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Hypoplastic or complete absence of thymus
Hypocalcemia (from no parathyroid) Recurrent infections w/ unusual organisms (fungi, large bacteria) |
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Severe combined immunodeficiency (SCID) (2, most common form)
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T and B cell deficiency (because B cells need T cell help)
Susceptibility to all infectious agents Mutation in IL-2R necessary for T cell proliferation in X-linked SCID |
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Wiskott-Aldrich syndrome (3 and treatment)
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SCID
Thrombocytopenia High IgE Treat w/ bone marrow transplant |
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Ataxia telangiectasia
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Ataxia
Telangiectasia - vascular defects, spider veins |
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How does HIV bind T cell
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HIV gp120 binds C4
gp41 binds CCR5 (chemokine receptor) |
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HIV diagnostic tests (3)
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Detect HIV Ab in blood
CD4:CD8 normally 2:1, reverses in HIV Measure serum HIV RNA to follow progress |
