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78 Cards in this Set
- Front
- Back
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Compromised immune system
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Anything from lack of a normal molecule to lack of entire populations of cells. From loss of function to gain of abnormal or excessive function.
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Immunity
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ability to resist infection.
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Professional immune system
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b cells, t cells, NK cells, DC, Granulocytes (neutrophils, eosinophils, basophilsmonocytes.
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Process that results from an immune response
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inflammation.
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An innocuous substance could cause
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an allergy or no response.
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The main rule of the immune response
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Remove the pathogen or the antigen.
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In infections
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both the pathogens and the responses cause tissue damage.
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Outcome of an immune response
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anything from a small nuisance to a fatal disease.
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In hypersensitivity
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the antigens are not destructive, but the responses to them cause tissue damage.
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Hypersensitivity reactions have Two separate mechanisms
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First one that generated the effector cells and molecules that then produce. The second, responsible for the tissue damage.
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The hypersensitivity reactions are classified on the basis
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of the mechanisms of tissue damage.
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Most hypersensitivity reactions depend on the production of
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antibodies.
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Type I hypersensitivity reactions are mediated by
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IgE and requires repeated exposure to allergen.
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Initial IgE production is favored by
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low antigen (allergen) dose, Generally, high initial antigen dose induces tolerance, Incidence is increasing in developed countries.
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Most allergens are
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small, soluble proteins carried on dried particles such as pollen, mite feces, or parasite enzymes.
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Type I, What cells pick up the allergen?
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Antigen presenting cells (mainly DC, Mph).
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Type I, Where does it have to be delivered?
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Secondary lymphoid tissue.
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Type I, Which cells have to pay attention?
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B cells, T helper cells.
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Type I, Important cytokines?
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IL-4, IL-13 to help B cells switch to IgE from IgM, IL-5 directed at activating eosinophils .
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Mast cell activation
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IgE binds to FceR (receptor on mast cell), allergen cross-links them. Immediate allergic reaction (evident by 30 min, lasts ~ 1hr). Late phase response (recruited eosinophils, basophils, Th2 cells) – develops in 2-24 hrs.
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Type I reaction
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Basically after crosslink to receptor signal are sent out for degranulation, phospholipaseA2 and cytokine activation in MAST CELL. All hell breaks loose, granules release histamine, protease, chemotactic factors, ECF, NCF. Cytokines. Phospholipase to arach acid and PAF, Arach acid to Leukotrienes (b4, c4, d4) and prostaglandin.
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Type 1 reaction primary mediators
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histamines, proteases, chemotactic factors (ECF and NCF)= immediate reaction.
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Type 1 secondary mediators
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Leutrienes (b4, c4, d40) and prostaglandins (d2)= last phase response.
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Type I Hypersensitivity Reaction Examples
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Localized: Allergic rhinitis, Asthma, Gastroenteritis, Skin: wheel and flare, hives, Sneezing, coughing, swelling, vomiting, abdominal cramps, diarrhea, trouble breathing, fainting. Systemic administration of allergen: Anaphylaxis Edema (including larynx, lungs, etc.), Bronchial constriction, Widespread vascular dilatation and leakage with drop in blood pressure.
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Atopy
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a predisposition to develop localized immediate hypersensitivity reactions to inhaled and ingested antigens. Tendency to have:High serum IgE, More IL-4-producing TH2 cells, 50% of patients have a family history of allergies, Genetic studies ongoing.
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Type II Hypersensitivity Reaction
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Cell surface-bound IgG.Cell (or matrix)-bound antibody, complement, phagocytes, NK cells, simple blocking of an important structure. IgG-mediated destruction of red blood cells (leading to hemolytic anemia) or platelets (leading to thrombocytopenia). Important: Side effect of some drugs, including penicillin
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Type III Hypersensitivity Reaction
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Antigen-IgG immune complex-mediated. Local response is called arthus reaction. Systemic response is called serum sickness, systemic, sometimes chronic supply of antigen (viral hepatitis, bacterial endocarditis), fevers, rash, arthritis, nephritis. Autoimmune conditions.
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Type IV Hypersensitivity Reaction
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Cell-mediated, Delayed type hypersensitivity, Insect venom, mycobacterial molecules (PPD), Swelling, erythema
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Autommunity
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The case of broken tolerance.
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Autoimmune disease
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Contribution of multiple factors:Genetic background, Environmental factors (infections), Auto-reactive B cells, T cells, Professional Antigen Presenting Cells, Cytokine combination.
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Type II autoimmune disease
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Pemphigus vulgaris, mucous membrane pemphigoid, acute rheumatic fever, Wegener’s granulomatosis, Goodpasture syndrome, Graves disease, myasthenia gravis, autoimmune hemolytic anemia, pernicious anemia.
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Type III autoimmune disease
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Systemic lupus erythematosus, post-streptococcal glomerulonephritis, polyarteritis nodosa, serum sickness.
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Type IV autoimmune disease
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Insulin-dependent diabetes mellitus, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, Sjogren’s syndrome.
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SLE causes
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complement activation leading to chemotactic factor leading to neutrophils leading to phagos leading to lysosomal enzymes to necrosis. Also platelet aggreg to microthrombi to ischemia. Also complement to anaphylatoxin to vasodilation and edema.
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SLE symptoms
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butterfly rash on face after sun, stiff fingersand hips in morn.
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SLE mechanism
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Anti-nuclear antibody production is T cell-dependent, Broken T cell tolerance to self-antigens, Antigen-antibody complexes deposit in kidneys and joints (small vessels), fix complement and tend to deplete C3 (low on blood tests), Photosensitivity not understood, has to do with UV effects on cells in skin, Management required corticosteroids to suppress immune responses.
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Discoid Lupus Erythematosus (DLE)
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Limited to skin or mucosa, Does not progress to SLE, >30% SLE patients have DLE lesions, Photosensitive (worse with sun exposure).
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Type IV: Rheumatoid Arthritis
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80% caucasoid patients have HLA-DR1 or HLA-DR4, Chronic inflammation of synovium: activated T cells, macrophages and plasma cells, Progressive destruction of cartilage and bone, Multiple joints, TMJ involved in 50-60%. Advanced disease: Deformity, ankylosis, With other autoimmune diseases (Sjogren, SLE, etc.), Other systems involved: Vessels, pericardium, pleura, subcutis, secondary lymphoid organs.
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Rheumatoid Arthritis
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Rheumatoid factor: IgM against IgG Fc (immune complexes). Joints: Cytokines IL-1, IL-6, and TNFa and chemokine IL-8 are dominant. Anti-TNFa treatment using antibodies results in long-term remission. Can Cause bone resorption as in mandi condyle.
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Requirements for pathologic autoimmunity (disease)
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1. Immune response to self-antigen, 2. This response is the primary pathogenic process (not just result of tissue damage in a normal immune response to an exogenous insult), 3. There is no other known cause for the disease.
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What does tolerance mean?
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Central: Stop killing off “overambitious” T and B cells, Genetic problems. Peripheral: Stop inducing anergy in B and T cells, Interfere with regulatory T cells, Prevent activation-induced death in B and T cells, Release antigens from immune-privileged sites.
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Autoimmune Diseases: Infections as Triggers
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During infections, APC may present self-antigens AND express co-stimulatory receptors to activate T cells (no anergy), Self-antigens can be released during responses to infections and stimulate B cells, B cells also express TLR, Microbial antigens may mimic self-antigens (molecular mimicry).
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Autoimmune Diseases: Causal Environment
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UV light. Drugs, Complicated. Hormones, Female and male, Example: SLE is 10 times more likely in females than males
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Autoimmune disease
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Tissue/organ damage as a result of an immune response against ‘self’ (broken tolerance).
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Autoimmune Diseases: Genetic Susceptibility Genes
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MHC are the best studied. Microbial recognition genes (NOD-2). Inhibitors of activation or of activated cells, Signaling molecules (PTPN-22), Regulators of adaptive responses (cytokines/receptors, apoptosis regulators, regulatory T cells).
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Autoimmune Disease: Genetic Associations
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Ankylosing spondylitis (B27), Pemphigus vulgaris (Ashkenazi Jews, DR4), Primary Sjögren syndrome (DR3-cauc.), Rheumatoid arthritis (DR4).
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Disease abbreviations
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DM – Diabetes Mellitus, MG – Myasthenia Gravis, MS – Multiple Sclerosis, RA – Rheumatoid Arthritis, Scl – Systemic Sclerosis, SS – Sjögren Syndrome, SLE – Systemic Lupus Erythematosus, ThD – Thyroid Disease.
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Autoimmune Disease Induction: Examples of Viral Infections
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Cross-reactivity to viral and self-antigens in EBV, HCV, CMV, HIV, mumps, etc., Insulin-dependent diabetes mellitus clusters with rubella, CMV and Coxsackie infections, HCV infection is often associated with lichen planus, erythema multiforme, etc.
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Autoimmune Disease Induction: Examples of Bacterial Infections
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Acute rheumatic fever, Antibodies to streptococcus cell wall antigens react with cardiac antigens. Wegener’s granulomatosis , IgG auto-antibodies to neutrophil antigens (Anti-Neutrophil Cytoplasm Antigen antibodies) attack neutrophils during infections, when cytokines induce the expression of the antigen on the cell surface, Serine Proteinase 3 (90-95%).
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The dominant cells and molecules in a particular immune response to infections depend upon
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how and where the pathogen infects the host: Viruses: Intracellular pathogens, lytic vs. latent infections. Bacteria: Intracellular and extracellular pathogens, Fungi: superficial vs deep infections. Multicellular parasites: cavities and tissues.
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Primary Immunodeficiencies
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Congenital, most are inherited, Generally present in young children, Often significant family history, Some are combined with other congenital defects. Almost always genetically determined. Most common is IgA deficiency. > then 150 identified. Caused by B or T or B and T cells (adaptive immune system), or Phagocytes, compliment. (Innate immune system).
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Secondary Immunodeficiencies
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Induced by environmental, infectious or iatrogenic factors, Common factors are malnutrition, HIV infection, radiation, chemotherapy, cancer, other illnesses. Complications of infections, Malnutrition, Aging, Iatrogenic (treatment-induced).
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Primary Immunodeficiencies: Severe Combined Immunodeficiency (SCID)
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Genetic abnormalities (autosomal or X-linked). Lymphopenia, agammaglobulinemia, lack of tonsils, lack of lymph nodes, Bacterial, viral, and fungal infections, Treatment: Bone marrow transplant (up to 95% survival)
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Primary Immunodeficiencies: B cells
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X-linked agammaglobulinemia of Bruton
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Primary Immunodeficiencies: X-linked Hyper-IgM Syndrome
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70% due to mutation in gene for T cell surface molecule that is needed for CD4+ T cells to communicate with Ag-specific B cells, as well as with DC, macrophages (CD40L).
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Leukocyte Adhesion Deficiency (LAD)
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Loss of cellular “Velcro”: Susceptibility to bacterial infections (skin, mucosa).
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Primary or secondary neutropenia: Features
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Bacterial infections, Staph aureus, gram-negative bacteria in middle ear, oral cavity, perirectal area. Gingival ulcerations.
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Examples of phagocyte deficiencies
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Agranulocytosis, Deep, punched-out ulcerations of buccal mucosa, gingiva. Clinically gingival lesions are similar to acute necrotizing ulcerative gingivitis.
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Immunodeficiency Secondary to HIV Infection: Mechanisms
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Persistent T cell activation leads to increased depletion rates.
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Diabetes Mellitus Leads to
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Secondary Immunodeficiency. Accumulation of glycosylation products in vessel walls, Affect cell traffic, function, Trap Ig, complement. Vessels of all sizes, Atherosclerosis, thickening of small vessel walls.
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Diabetes Mellitus: Immunodeficiency Mechanisms
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T cell function: depressed. Neutrophil function depressed, Adherence, chemotaxis, phagocytosis, anti-oxidant activity. Common infections: Bacterial (Strep. pneumoniae, Staph. aureus, H. influenzae, E. coli, other Gram -, anaerobes), Fungal (candida, rhizopus), Oral problems: accelerated periodontal disease, poor healing, candidosis.
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HIV Infection: Immune System Abnormalities
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Lymphopenia. Decreased T cell function, Susceptibility to infections, neoplasms, Loss of activated and memory T cells, Decreased helper, cytotoxic, and other activities.Polyclonal B cell activation, Decreased monocyte/macrophage functions.
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Secondary immunodeficiency due to HIV infection
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Candidosis, Deep fungal infections, Pulmonary TB, atypical TB, Recurrent pneumonia, Cytomegalovirus (CMV), HSV longer than 1 month, Kaposi’s sarcoma (<60yrs), Lymphoma of brain (<60 yrs).
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Immunodeficiency Secondary to HIV: Mechanisms
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Infected cells: CD4+ T cells, dendritic cells, monocytes/macrophages, Receptor: CD4, co-receptors: CCR5, CXCR4. Clinical latency: Active viral replication in lymphoid tissue, spreading from cell to cell.Sustained increase in all lymphocyte turnover, persistent immune activation. Measurement of AIDS development: CD4+ cell counts, viral load, activation markers on CD8+ T cells. Persistent T cell activation leads to increased depletion rates. Depletion of T cells due to cytopathic effect of the virus.
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Diabetes Mellitus Leads to Secondary Immunodeficiency
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Susceptibility to skin infections, TB, pyelonephritis, pneumonia, Cause death in 5% of diabetic patients.Accumulation of glycosylation products in vessel walls affects cell traffic and function, trap Ig, complement.Atherosclerosis, thickening of small vessel walls leads to poor delivery of white blood cells .
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Diabetes Mellitus: Immunodeficiency causes
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T cell function is depressed. Macrophage cytokine production is decreased. Neutrophil function is depressed, Adherence, chemotaxis, phagocytosis, anti-oxidant activity. Common infections: Bacterial (Strep. pneumoniae, Staph. aureus, H. influenzae, E. coli, other). Fungal (candida, rhizopus). Oral problems: accelerated periodontal disease, poor healing, candidosis.
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Iatrogenic Cause of Immunodeficiency
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immunosuppressive drugs.
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Amyloidosis
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Deposition of proteins in tissues causing dysfunction. Various forms, Hereditary – not immune-mediated, Primary amyloidosis: associated with immune system cell disorders, Secondary amyloidosis – complication of chronic inflammatory conditions. Some infections, rheumatoid arthritis, other.
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Autoimmune Diseases, Genetic Susceptibility Genes
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MHC are the best studied. Microbial recognition genes (NOD-2). Inhibitors of activation or of activated cells, Signaling molecules (PTPN-22), Regulators of adaptive responses (cytokines/receptors, apoptosis regulators, regulatory T cells).
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What is HANES?
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Hereditary AngioNeurotic Edema.
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Phagocyte deficiencies: Susceptibility to bacterial infections with chronic granulomatous inflammation if ?
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There is a defect in ability to kill bacteria (all phagocytes).
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Phagocyte deficiencies: Susceptibility to bacterial infections without granulomatous inflammation if
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Defect in the ability to bring enough phagocytes (neutrophils especially) to the site of infection.
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What are the Asplenia Consequences?
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Spleen is critical for mounting an antibody response to new infections with encapsulated bacteria that enter the blood stream (H. influenzae, Strep. pneumoniae). As long as antibodies are present, they will opsonize encapsulated bacteria and the Kupfer cells in the liver will then remove the bacteria. Requires additional immunizations and prophylaxis with antibiotics before dental treatment.
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Hereditary Angioneurotic Edema?
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Absence of the C1 inhibitor C1INH leads to uncontrolled activation of the classical complement pathway. One consequence: overproduction of the vasoactive C2a fragment, causing the accumulation of fluid in the tissues, but no cells get out. No pain or itching, because the process does not go so far as to involve C3 and C5 – no inflammation.
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Skin tests are useful __ hrs after anaphylaxis
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96.
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Hashimoto thyroiditis
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IgG, TH1 and cytotoxic T cell-mediated disease that induces inflammatory destruction of the thyroid with loss of function.
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Graves disease
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IgG-mediated disease that induces thyroid hypertrophy and hyperplasia with hyperfunction.
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Poison ivy Mechanism
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Type IV hypersensitivity (cell mediated). Antigen: pentadecacatechol. Covalent binding to skin cell proteins (hapten).Langerhans cells phagocytose/pinocytose the material, process and present the modified proteins.
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