Microbiology - Hs

Front 1

Define Hypersensitivity

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An excessive or abnormal secondary immune response to a sensitizing agent

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Case: play Frisbee outside. fall and landed in weedy area. 2 days later notice that distal legs and arms are covered with a red, raised rash that is very itchy (pruritic). Question - 1. what is this? 2. why did you get this? 3. why did teh rash take 48-72 hours to develop? 4. how could you have avoided this? 5. what form of hypersensitivity is this? 6. how can you treat it?

Back 2

1. poison ivy; 2. contact; 3. Type IV HS have delayed response; 4. if washed off oil with water right away, it would have been ok; 5. Type IV hypersensitivity; 6. Steroids

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Hypersensitivity Type I - prototype disorder (ex) & immune mechanism

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1. Anaphylaxis, some form of bronchial asthma; 2. Formation of IgE (cytotropic) AB --> immediate release of vasoactive amines and other mediators from basophils and mast cells followed by recruitment of other inflammatory cells

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Hypersensitivity Type II - prototype disorder (ex) & immune mechanism

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1. Autoimmune hemolytic anemia, erthroblastosis fetalis, Goodpasture syndrome; 2. Formation of IgG, IgM --> binds to antigen on target cell surface --> phagocytosis of target cell or lysis or target cell by C8,9 fraction of activated complement or antibody-dependent cellular cytotoxicity

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Hypersensitivity Type III - prototype disorder (ex) & immune mechanism

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1. Arthus reaction, serum sickness, systemic lupus ertyematosus, certain forms of acute glomerulonephritis; 2. Antigen-antibody complexes --> activated complement --> attracted neutrophils --> release of lysosomal enzymes and other toxic molecules

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Hypersensitivity Type IV - prototype disorder (ex) & immune mechanism

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1. Tuberculosis, contact dermatitis, transplant rejection, poison ivy; 2. Sensitized T lymphocytes --> release of lymphokines and T cell-mediated cytotoxicity

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Type II Hypersensitivity - 1. General process; 2. How does dz develop from drugs?

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1. Involves AB (IgG or IgM) binding to cell or matrix bound antigen (can't be soluble antigen) --> phagocytic or NK cells bind to the AB via their Fc receptor (Fcgamma-RI) --> The target tissue is then destroyed. Complement may be involved (increases binding via C'receptors on phagocytic cells); 2. Some drugs (penicillin, quinidine, or methyldopa) may become antigenic when bound to erythrocytes or platelets (make epitope not existing before) --> in some individuals IgG may be made against the combined drug-cell antigen --> destruction of the erythrocytes (hemolytic anemia) or platelets (thrombocytopenia) may then develop with the spleen as the major site of cell destruction. * IgG does not react with free drug, just the cell-bound version

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Hemolytic Anemia - definition, process of development

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Destruction of erythrocytes. Type II Hypersensitivity dz (IgG made against combined cell-drug antigen)

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Thrombocytopenia - definition, explain

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Destruction of platelets. Type II Hypersensitivity dz (IgG made against combined cell-drug antigen)

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Type II Hypersensitivity reactions - dz examples

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Goodpasture syndrome, Bullous pemphigoid, pernicious anemia, vasculitides, thrombotic phenomena, acute rheumatic fever

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Good pasture syndrome - what type of HS?

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Type II HS. Sx - Nephritis and lung hemorrhages. Px - AB targeted against the type IV collagen in basement membranes of glomeruli and lung alveoli

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Bullous pemphigoid - what type of HS?

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Type II HS. Sx - skin vesicles (generalized cutaneous lesions and involvement of mucosal surfaces. Subepidermal, nonacantholytic blister). Px: autoimmune dz AB specific for epidermal basememt membrane proteins. Linear disposition of IgG AB and complement in the BM zone. (Robbins 846)

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Pernicious anemia - what type of HS?

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Type II HS. Megaloblastic anemia (Very large blood cells but not many of them). Vitamin B12 (Cobalamin) deficiency. Autoimmune disorder - AB that bind to intrinsic factor and gastric parietal cells. (Robbins 438)

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Vasculitides - what type of HS?

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Type II HS. Varied clinical features. AB specific for Neutrophil cytoplasmic antigen. (ANCA). (R. 362)

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Thrombotic phenomena - what type of HS?

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Type II HS. Varied clinical featurs. Antiphospholipid AB (clot more easily)

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Acute rheumatic fever - what type of HS?

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Type II HS. Myocarditis, arthritis. AB that targets Strptococcal cell wall antigen, AB cross-reacts with myocardial antigen. --> inflammation, macrophage activation

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Case: You are called to the bedside of a patient who is receiving a blood transfusion. Shortly after the transfusion started, she began to have a fever, developed chills, started sweating and began to look pale. Her heart rate is elevated and her pulse is thready. why is this?

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Type III Hypersensitivity

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Type III Hypersensitivity - cause & result, Pathophysiology

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Due to the production of IgG against a SOLUBLE antigen. An antigen-antibody immune complex then forms adn activates complement. The immune complexes can cause damage both by activating FcgammaR expressing cells as well as activating complement at sites of deposition (Large complexes are usulaly cleared by phagocytic cells. Small lcomplexes - when antigen is in excess - tend to precipitate on blood vessel walls, where leukocytes may be activated by binding them. / Damage usually in kidneys, vessels, joints, and skin / Circulating complexes fix complement. Deposition of complexes (preference for sites with increased vascular permeability. Areas where hemodynamic parameters support deposition - pressure-gradients and bifurcations (so they can precipitate). Sites of increased antigen -- increased production in situ. antigen tissue preference). Phagocytic cell influx (neutrophil predominant). Activation of phagocytes with release of lysosomal enzymes. Resultant tissue destruction.

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Type III HS - examples

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Arthus reaction, Serum sickness, Farmer's lung, Systemic antigen excess situations

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Arthus reaction

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Type III HS. Name given to a reaction seen in the skni when sensitized individuals are exposred to specific antigen. involves activation of mast cells and other leukocytes primarily via Fc-gamma-RIII and not complement (although complement may participate)

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Serum sickness

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Type III HS. A systemic reaction from injection of large quantities of foreign protein (Antiserum from horse, Anti-thymocyte globulin, streptokinase). Initially occurs 7-10 days after exposure to antigen (this is the time needed to switch from IgM to IgG). Flu-like sypmtoms with an urticarial rash, arthritis, and glomerulonephritis. Repeat exposures are associated with a much shorter course to onset of symptomes. (See graph - Foreign serum proteins + AB against foreign serum proteins = Ag-AB complexes / lowering either one reduces effect)

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Farmer's lung

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Type III HS. An alveolitis due to a type III rxn against hay dust or mold spores. May lead to inflammation in and destruction of the alveolar wall with impairment in gass exchange.

Front 23

What type of disease is Farmer's lung?

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Hypersensitivity type III

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Systemic Antigen excess situations (Autoimmune diseases like Lupus, infections - Viral hepatitis or subacute bacterial endocarditis. Recurrent antigen production)

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Hypersensitivity type III

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CAse: Patient with Systemic Lupus Erythematosus (SLE). Patients with SLE make AB against DNA, nucleoproteins, adn other self proteins. They develop arthritis, glomerulonephritis, and skin disease amonst other target organs: Question - 1. Why would someone with SLE develop disease at these organ sites? 2. What type of immune response does this respresent? 3. Would removal of AB be helpful in this disease?

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It is Hypersensitivity Type III. Antinuclear AB. Removing AB would be useful. [R.139]

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Type IV hypersensitivity - characteristics. mediators

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Does not involve AB. Antigen enters the skin (usual target organ) and then binds to self proteins. --> this bound antigen must then be taken up and processed by APC that present antigen to T cells. Requires 24-72 hours to develop. Involves CD4+ Th1 cells or CD8+ Tcells. / IFNgamma (induces expression of adhesion molecules. Activated macrophages). TNFalpha & LT (local tissue destruction, induces expression of adhesion molecules. IL-3 and GM-CSF (stimulate monocyte production from bone marrow. Chemokines (recruit macrophages to site.

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TYpe IV HS - disease

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Tuberculin response, Contact dermatitis

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Tuberculin response

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Type IV HS. M.Tuberculosis derived peptides are injected into the skin and in previously exposed individuals a Th1 mediated response develops with swelling at the injection site in 48-72 hours.

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Contact dermatitis

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Type IV HS. caused by chemical exposure to skin. The compounds then bind with self proteins and generate a response with extensive macrophage mediated inflammation. Is the etiology of the poison ivy rash, or Rhus Dermatitis. (Due to pentadecacatechol, a lipid-soluble chemical in the plant leaf)