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Urticaria & Eczema

Clinical manifestations of immediate hypersensitivity reactions (type I) as: Urticaria (hives) Eczema in the skin Forms of Type I Disease: Urticaria (hives), eczema, conjunctivitis, rhinitis (hay fever), asthma, and anaphylaxis (bronchoconstriction & hypotension can be life threatening) Mediators: Histamine, slow reacting substance of anaphylaxis (SRS-A), eosinophil chemotactic factor of anaphylaxis (ECF-A), serotonin, prostaglandins, thromboxanes



Preformed in granules of tissue mast cells and basophil It causes: vasodilatation, increased capillary permeability, smooth muscle contraction Smooth muscles of the bronchi and intestines will be contracted as well Blood vessel will increase permeability to content of blood vessels will leave Preformed mediator that exists in the granules and immediately released to have an effect


SRS-A (leukotrienes)

Several leukotrienes that are not preformed and released during anaphylactic reactions (later) SRS-A = Slow reacting substance of anaphylaxis Synthesized from arachidonic acid thru lipoxygenic pathway Increase vascular permeability and smooth muscle contraction Main mediators of bronchoconstriction of asthma



Eosinophil chemotactic factor of anaphylaxis Tetrapeptide Preformed in mast cell granules Attracts eosinophils, which are involved in antiparasitic action and release histaminase (degrades histamine) and arylsulfatase (degrades SRS-A (leukotrienes)) Eosinophil, therefore, reduces severity of type I response During Type I hypersensitivity, it will be released and attract eosinophils, which produce its own products from its granules to add to the actions during the hypersensitivity reaction Mast cells are activated and release the contents, and it will immediately bring eosinophils which released histaminase and arylsulfatase which degrade histamine and leukotrienes so really eliminate the mediators of the hypersensitivity reactions Beneficial when fighting parasites and for the patient so the hypersensitivity reaction does last forever/reduce severity



Preformed in mast cells and blood platelets Derived from tryptophan Role in anaphylaxis considered minor: capillary dilatation, increased vascular permeability, smooth muscle contraction


Prostaglandin & Thromboxane

Related to leukotrienes Derived from arachidonic acid via cyclooxygenase pathway (not pre-formed) Prostaglandin effects: dilation, increased permeability, bronchoconstriction Thromboxanes: aggregate platelets causing the occlusion of blood vessels


Anaphylactoid Reaction

Clinically similar to anaphylactic reactions Different mechanism- not IgE mediated and mast cells mediators release directly induced by drugs and iodinated chemicals


Drug Hypersensitivity

Antibiotics most common agents allergic reactions Metabolic products of the drug act as haptens Hapten binds to host protein, becomes immunogenic sensitizing Ag, production of IgE, which coat mast cells Re-exposure to the drug (allergen) leads to binding allergen to IgE coat and degranulation of mast cell leading to type I hypersensitivity Clinical symptoms: rash, fever, local or systemic anaphylaxis with varying severity Drug sensitivity skin test


IgE-Mediated Renal Penicillin Allergy

Allergic tubulointerstitial renal disease due to penicillins is associated with: Penicillin or its metabolic products act as haptens IgE deposition on mast cells  activation Eosinophilia Eosinophilic infiltration in the kidney Responsiveness to corticosteroids Rapid improvement after discontinuation of the causative drug



Includes type I reactions exhibiting familial predisposition Associated with high levels of IgE Genetically based disorders Induced by exposure to specific allergens like pollens,, dust, and food Common symptoms: urticaria, eczema, asthma, hay fever The skin tests for the individuals with atopy are immediately positive when specific antigens are used Atopic allergy is transferable by serum only It is antibody-mediated Probable cause:reduced numbers of suppressor T cells and predisposition to an abnormally high IgE response


Prausnitz-Kustner Reaction (obsolete test)

Test was used in the past to determine the cutaneous anaphylaxis Serum from atopic patient was taken and injected into the skin of a normal person A few hours later the test antigen was injected into the sensitized site (in the normal person) Positive results: immediate type of wheal-and-flare reaction Not used anymore- danger of transmitting viral infections


IgE in Anti-parasitic Activity

IgE produced and inserted themselves at the Fc receptor on the mast cells, and when the next wave of allergens comes along it will activate the mast cell which will release their granules and release chemotactic factor, which will go into the blood vessels (ECF-A) and attract eosinophils and they accumulate in the area of action is around the mast cell which is associated with the worm Histamine will dilate the vessel and increase the permeability so everything can get to the worm to defeat it Eosinophils attach to the worm, so we have a worm coated with eosinophil which will release the granules on the worm killing it and released as feces


Type II Hypersensitivity: Ab Mediated

Ab directed towards cell surface Ags RBC surface Ags preferred targets, but IgE not involved IgG or IgM: attaches with specificity to Ag via Fab region and acts as a bridge to complement via the Fc region Complement activation = complement-mediated lysis NK can participate by ADCC Examples: hemolytic anemia, ABO transfusion reactions, Rh hemolytic disease Antibodies (other than IgE) may cause tissue injury and disease by binding directly to their target antigens in cells and extracellular matrix


Effector Mechanisms of Ab-Mediated Diseases

Abs may cause disease by inducing inflammation at the site of deposition Abs that bind directly to their target Ag (type2) has 3 mechanisms : complement activation and recruitment, FcR mediated recruitment, activation of inflammatory cells Immune complexes cause disease mainly by inducing inflammation Abs may cause disease by opsonizing cells for phagocytosis and interfering with normal cellular functions like hormone receptor signaling, plus C3b complement product=opsonin All three mechanisms are seen with antibodies that bind directly to their target antigens Examples: Myasthenia Gravis involves Ab directed towards the ACh RECEPTOR so ACh cannot bind to the receptor so the signal from the nerve cell to the muscle cell so the muscle will not activate and will remain relaxed and weakens; IgG can cross the placenta Productions of Ab directed against the TSH RECEPTOR to cause Graves Disease to cause constant activation and release of T3 and T4 = hyperthyroidism


Type II: Drug Adverse Reactions

Quinine (Anti-malarial): attach to platelets and induce auto-Abs formation; can cause thrombocytopenia and bleeding because less thromobocytes than normal Hydralazine (antihypertensive drug): modification of host tissues, production of anti-DNA auto-Abs; SLE-like symptoms


Type II: Autoimmune Diseases

1. Rheumatic fever: Abs against Group A streptococci cross-react with cardiac tissue (M cells) 2. Mycoplasma pneumoniae infection: Abs are formed that cross-react with RBCs, which results in hemolytic anemia 3. Goodpasture syndrome: Abs to basement membrane of the kidneys and lungs are formed, which leads to severe damage to the membrane via complement-attracted leukocytes 4. Pernicious Anemia: Ag target is intrinsic factor of gastric parietal cells, and the disease neutralizes intrinsic factor and decreases absorption of B12 causing abnormal erythropoiesis (anemia) 5. Pemphigus vulgaris: Ag target are epidermal cadherins causing interruption of intercellular adhesions resulting in skin vesicles 6. Hemolytic Anemia: Rh blood group Ag are targets causing opsonization and phagocytosis of erythrocytes resulting in bleeding and anemia


Type III Hypersensitivity: Immune Complex Mediated

Abs IgG and IgM may cause tissue injury & disease by forming immune complexes that deposit in blood vessels Ag-Ab complexes induce an inflammatory response in tissues, and instead of being removed, Ag-Ab complexes persist and deposit in the tissues Persistent infections lead to depositing immune complexes in the kidneys, joints, and lungs ==> damage The complex will activate the complement, C3b and MAC produced; opsonin – macrophage and other cells and we will have recruitment of C5a which recruits the neutrophil and other WBCs causing an inflammatory reaction to damage all the cells in that area to cause hemorrhage/bleeding


Type III Hypersensitivity: Autoimmune Mech

Self Ags elicit production Abs and bind to an organ, antigen, or deposit in organs as complexes Joints causing arthritis Kidneys causing nephritis Blood vessels causing vasculitis Immune complexes activate complement, attract PMNs by C5a causing inflammation and tissue damage


Type III Hypersensitivity: Autoimmune Diseases

1. SLE: Ab against DNA and nucleoproteins resulting in nephritis, arthritis, and vasculitis 2. Polyarthritis nodosa: Ab against Hep B virus surface Ag causing vasculitis 3. Post-streptococcal Glomerulonephritis: Ab target streptococcal cell wall Ag causing nephritis Mechanism for all 3: complement and Fc receptor mediated inflammation


Type III Hypersensitivity: Serum Sickness

Allergic reaction to foreign serum (antiserum) and proteinaceous drugs When you take the antiserum containing Ab, but also contains proteins and Ab for the recipient are considered Ag because they are foreign so the patient may form a reaction with this serum Recipient of antiserum responds with Ab production Ag (from antiserum) + Ab forms the Ag-Ab complex causing inflammation and serum sickness with symptoms- 1-3 weeks later with fever, urticaria, lymphadenopathy, arthralgia, hives, itching Serum sickness: occurs when anti-serum used to treat something like tetanus, botulism, rabies, and other exotoxins that produce diseases Also from injections of monoclonal Ab to treat cancer or anti-T cells Ab to prevent graft rejection Small-molecule drugs that act as haptens: penicillin- elicits IgG production, sulfa drugs, Cefaclor Complications: Angioedema- Swelling, anaphylactic shock, vasculitis Not common now because of the dangers of the antiserum containing viruses and so on


Type III Hypersensitivity: Arthus Reaction

Local inflammatory reaction with necrosis By using foreign serum in the skin rather in the circulation to treat disease Occurs after few hours of intradermal Ag inoculation Recipient of injection must be sensitized- previously vaccinated with vaccine that requires multiple doses Abs from previous vaccination form complex with Ag at site of injection causing cell necrosis, local inflammation, “Localized serum sickness”


Type IV: Cell Mediated (Delayed Type Hypersensitivity)

Starts days after contact with allergen and lasts for days DTH elicited by: innocuous substances, prime defense mechanism against intracellular bacteria and fungi, mechanism in many viral infectious diseases Immunity assessed by serologic tests and more specific than skin tests Helper (CD4) T lymphocytes take time to activate other cells to do the damage -delayed response Sensitized T cells transfer transfers the hypersensitivity Reaction: T helper activate macrophages = induration as seen in poison ivy T helper and cytotoxic cells


Type IV: Mechanisms of Tissue Injury

T cells may cause tissue injury and disease by 2 mechanisms Delayed hypersensitivity reactions, which may be triggered by CD4+ and CD8+ T cells and in which tissue injury is caused by activated macrophages and inflammatory cells Direct killing of target cells, mediated by CD8+ CTLs


Diagnostic Circulating Tumor Markers

Circulating tumor markers are diagnostic: i. α-fetoprotein hepatic carcinoma ii. Carcinoembryonic Ag (CEA) colorectal carcinoma iii. GM1 monosialoganglioside in 96% of patients with pancreatic carcinoma


Monoclonal Ab (mAB) to Tumor Surface Ag: Targets

Monoclonal Ab to tumor surface antigens can provide a basis for imaging. Good targets include: i. F19 glycoprotein on reactive stromal fibroblasts ii. Certain tumor mucins/epithelial cancers (T antigen) iii. Cytokeratin on carcinoma cells


Detection of Bone Marrow Micrometastasis

Detection of bone marrow micrometastasis using immunocytochemistry techniques provides information on: i. Prognosis ii. Efficacy of a new therapy iii. Eventual recurrence of treated cancer


Types of Grafts

Syngeneic grafts (syngraft/isograft): donor and recipient are genetically identical = No rejection Identical twins, inbred mice Their Ags are called isoantigens and have isoantibodies

Allogeneic grafts (allograft/homograft): donor and recipient are genetically different members of the same species = rejection Their Ags are called alloantigens Their Abs & T cells are alloreactive (alloantibodies)

Xenogeneic (xenograft): donor and recipient are from different species = Rejection Their Ags are called xenoantigens Their Abs & T cells are xenoreactive


Transplantation Laws

1. Autografts and Syngrafts are accepted 2. Allografts are rejected 3. Transplants from parent to F1 hybrid are accepted; reverse rejected 4. Transplants from F2 individuals to F1 are accepted* 5. Transplants from either parent are mostly rejected, but accepted in some


Recognition of allogeneic MHC molecules by T lymphocytes

1. Self MHC + foreign peptide = normal 2. Donor peptide recognized + Donor MHC that looks like self MHC not recognized = Direct Allorecognition 3. Donor peptide recognized + donor MHC recognized = Direct Allorecognition Direct Allorecognition: T cells bind directly Indirect Allorecognition: Donor MHC picked up by APC, which processes the peptide to present to T cells


Hyperacute Graft Rejection

In hyperacute rejection, preformed antibodies react with alloantigens on the vascular endothelium of the graft, activate complement, and trigger rapid intravascular thrombosis and necrosis of the vessel wall