Type II Imunopathology Flashcards
NIH recognizes
80 conditions of autoimmunity (but there are more). 5-8 per 100 in US have one or more of these.
immunopathology depends on 3 factors
genetics, environment and bad luck
5 pathological processes in all these conditions
they are must MECHANISMS, most actual disease have been found to involve more than one mechanism.
The mechanisms: Type I
Symptoms or pathology due to IgE antibody. Since the type of B-cell-helper Tfh cell that drives switching to IgE seems to be closely related to the Th2 cell, Th2-mediated events are often seen along with those caused by IgE.
The mechanisms: Type II
Pathology due to IgG, IgM, or IgA antibody causing harm to self. In most cases this refers to autoantibodies. Type V was separate; but it is now folded into Type II, as it involves autoreactive antibody against surface receptors which happen to stimulate (rather than damage) the cell.
The mechanisms: Type III
Pathology caused by the formation of immune complexes which are trapped in the basement membranes of blood vessels and activate complement, leading to vasculitic inflammation.
The mechanisms: Type IV
Pathologic outcomes of normal or abnormal (including autoimmune) T cell responses, including both helper and cytotoxic cells.
Chronic Frustrated Immune Responses.
It refers to conditions in which the body is using the adaptive immune response to try to get rid of antigens that it never can. These include things like normal gut flora (as in Crohn disease), skin flora (psoriasis), chemicals (as in chronic beryllium disease), or foods (gluten in celiac disease). The ANTIGEN can be neither disposed of nor effectively walled off.
Type II discussion
TYPE II. This form of immunopathology is due to the actions of antibodies directed against a specific target tissue, cell, or molecule; so it is one of the forms of AUTOIMMUNITY. There is also T cell-mediated autoimmunity, which is a part of Type IV immunopathology. Note that it’s technically a lot easier to detect specific autoantibodies than autoreactive T cells.
Complement-mediated damage.
Tissues against which antibodies are made can be damaged by lysis (red cells in autoimmune hemolytic anemia), by phagocytosis (platelets in autoimmune thrombocytopenic purpura) or by release of the phagocytes’ lysosomal enzymes and reactive oxygen species (probable in myasthenia gravis and Goodpasture disease). Also platelets can be opsomized and taken out.
Stimulatory Hypersensitivity
If the autoantibody happens to be directed against a cell- surface receptor, it may behave as an agonist, mimicking whatever hormone or factor normally works at that receptor. ►The classic example of this is the ‘long-acting thyroid stimulator’ found in the blood of most patients with hyperthyroidism. LATS, as it was called for a long time, is simply an IgG antibody to the TSH (thyroid-stimulating hormone) receptor on thyroid cells
Inappropriate tachycardia
a fast heart rate without cardiac abnormalities. About half have been shown to have autoantibodies to the β-adrenergic receptor, which are stimulatory, like epinephrine; the effect can be REVERSED by the beta blocker propranolol. Often seen in young women.
Myasthenia Gravis
Disease of progressive muscle WEAKNESS, because patients are making antibody to the acetylcholine receptor (AChR). ►The antibody to the alpha subunit of the AChR does the real damage, which is complement- and neutrophil-mediated. Neutrophil “burps” out bad stuff on the end of the receptors and then the AChRs get harder and harder to stimulate. SIGN - drooping eyelid is an early sign. TREATMENT: drugs that can increase duration of achtylcoline duration.
Rheumatic Heart Disease
Defined as heart disease occurring shortly after a streptococcal infection, for example a ‘strep throat.’ ►There is very good evidence that it is due to CROSS-REACTION between a Group A Streptococcus M-protein antigen and a structure on the heart’s endothelial lining, probably laminin on heart valves, followed by neutrophil-mediated tissue destruction. Often seen in kids since there immune system is not developed enough.
Rheumatic fever
is the same disease as Rheumatic Heart Disease with more widespread manifestations, including in the skin and CNS.
Dressler Syndrome
Most people who have a heart attack will make some AUTOANTIBODY which reacts with heart. This seems to do them no harm. Dressler syndrome manifests as persistent cardiac pain, fever, malaise, and pericardial effusion seen after heart attack (and more commonly after heart surgery) which is directly related to an immune response to pericardial or myocardial antigens. A better name might be post-cardiac injury syndrome. Treated with anti- inflammatory agents, it usually gets better as the heart heals. Referred to as sequestered.
GOODPASTURE SYNDROME
involves formation of ►autoantibodies to
lung and kidney basement membranes (BM) (which are the collagenous non-living connective tissue framework upon which the endothelial cells of capillaries sit). ►There is an antigen (Type IV collagen)sharedbetween the BM’s of these two organs, because other organs are not involved. The patients have persistent glomerulonephritis, and
pneumonitis with pulmonary hemorrhages (see coughing blood). In GOODPASTURE the antibody is directed against the basement membrane, not trapped as clumps, so the staining by immunofluorescence is sharp and ‘linear,’ not ‘lumpy-bumpy’ as it is in Type III, immune complex conditions.
AUTOIMMUNE THROMBOCYTOPENIC PURPURA (ATP)
These patients have bleeding abnormalities due to destruction of platelets (thrombocytes) by autoantibody;; ►the platelets are opsonized and their destruction, mainly in the spleen, is rapid.
AUTOIMMUNE HEMOLYTIC ANEMIA (AIHA)
Like ATP, this may follow a viral infection, or be associated with another autoimmune syndrome, or cancer. ►Many drugs, such as penicillin, methyldopa, chlorpromazine and quinidine, can induce AIHA, usually temporarily. In the rare condition paroxysmal cold hemoglobinuria (PCH), the patient experiences hemolysis after exposure to cold.
Systemic lupus erythematosus (SLE)
This is the classical multifactorial autoimmune disease, with both genetic and environmental causes and triggers;; but we still don’t understand it. Everything is going wrong. Many think it could be a disorder of the management of apoptotic cells. people with lupus may make antibody to: nuclear and nucleolar proteins; DNA; RNA; erythrocytes; clotting factors; platelets; skin; and T cells. ►MOST SEVERE SLE is where Antibody to double-stranded DNA is pathogenic, and may explain not just the kidney disease but also the characteristic facial butterfly rash, with local immune complex formation near sun-damaged, DNA-releasing skin cells. NOTE that antibody cannot get through cell membrane, so the interaction is will DNA in the blood, it makes complexes with antibody and then goes to the kidney and get lumpy bumby. TYPE III problem. Butterfly skin on nose is bc that is think skin and gets easily sun damaged.
Rheumatoid arthritis
It is the ‘inflammatory arthritis.’ RA affects women more than men, and usually attacks the smaller joints, especially those of the fingers, first. The initial evidence that it was autoimmune came with the discovery of rheumatoid factor (RF)(a rare antibody) which can be detected by adding the patient’s serum to microscopic beads that are coated with normal human IgG. RF makes the beads agglutinate; ►it is IgM, but it isanti-IgG! RA respond extremely well to rituximab, a monoclonal antibody against the CD20 on the surface of B cells, which effectively depletes them from the body.
HASHIMOTO THYROIDITIS.
An inflammatory disease of the thyroid in which there is very good evidence for both T and B cell immunity to various thyroid antigens, including thyroglobulin. The antibodies to thyroid antigens are destructive, not stimulatory. Histologically the thyroid is infiltrated by T cells. It may be that T cell damage allows antibodies access to normally sequestered antigens, which worsens the condition. The result is hypothyroidism.
Other diseases
There are often autoantibodies found in conditions that are known to be T cell-mediated; this indicated that immunity may be generally dysregulated. In celiac disease, there is an antibody to tissue transglutaminase that is very useful for diagnosis, and in Type 1 (childhood) diabetes several antibodies to islet-associated antigens are seen which provide prognostic information; but in neither of these conditions are they thought to be pathogenic,
Foreign + self hybrid
antigen
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