Immunology - Type II Hypersensitivity Flashcards
Definition
Cytotoxic hypersensitivity, tissue-specific antibody mediated destruction of cell in specific organ/tissue (type III would be systemic)
Central tolerance
Immune system should be able to determine self from non-self, defective cells undergo apoptosis in thymus (T-cells) or bone marrow (B cells)
Autoimmune disease
arises when a self-reactive cell (defective lymphocyte) attacks self
Self-reactive B cells
With CD4+ T-helper cells produces IgM and IgG that bind to intrinsic (normally made by host) and extrinsic (attach to host cell) antigens
Penicillin and RBCs - general
Usually antigen-antibody complex counteracts infection, when penicillin binds to RBC it becomes an extrinsic antigen, an IgG (more rarely IgM) specific to penicillin might bind causing antigen-antibody complex
Cytotoxic mechanism 1 - complement system (general)
Complement system = family of small proteins that work in an enzymatic cascade to fight off bacterial infections using a variety of mechanisms
Penicillin and RBCs - complement system
The IgG or IgM antibodies activate complement proteins which ultimately will kill the red blood cell bound to penicillin which is complexed now with IgG or IgM
Cytotoxic mechanism 1 - complement system (process)
C1 the first of the complement proteins binds the Fc portion of the antibody -> engages C2 through C9 (some of which are activated by being cleaved by an enzyme) -> cleaved fragments C3a, C4a, and C5a act as chemotactic factors, (attract certain cells in this case neutrophils) -> neutrophils degranulate (peroxidase+myeloperoxidase+proteinase 3 help generate oxygen radicals that are highly cytotoxic to cells and can cause tissue damage)
Effects of drug reactions
Hemolytic anemia (sometimes called autoimmune hemolytic anemia)+thrombocytopenia+neutropenia, since these are the blood cell types that are often affected
Goodpasture’s syndrome
antibodies bind to intrinsic antigens on collagen of the basement membrane in their glomeruli in the kidney or their alveoli in the lungs
Cytotoxic mechanism 2 - complement system membrane attack complex (MAC)
C5b + C6-C8 and a bunch of C9 come together to form the membrane attack complex -> inserts itself into the cell membrane creating a channel that allows fluid and molecules to flow in and out of the cell -> due to the osmotic difference fluid rushes into the cell -> cell lysis
Direct Coomb’s test
for autoimmune hemolytic anemia, the person’s RBCs are separated from the plasma and mixed with Coombs reagent which is anti-human globulin: agglutination = RBCs probably have antibodies on the surface
indirect Coomb’s test
check for blood group incompatibility, patient’s serum is mixed with laboratory RBCs with known antigens on their surface and Coombs reagent, blood cells agglutination = antibodies or complement in serum, prevent mismatched blood transfusion or a second pregnancy with a mismatched Rh factor between mother and child
Cytotoxic mechanism 3 - opsonization
IgG antibodies coat a blood cell and are bound by C3b, cell is opsonized which means it’s targeted for phagocytosis (engulfed and destroyed by phagocytes like macrophages and neutrophils), antigen-antibody complex and the cell it’s attached to encounters a phagocyte in the spleen which targets cells by binding to the Fc tail of the antibody or the C3b bound to the IgG
Cytotoxic mechanism 4 - antibody-dependent cell-mediated cytotoxicity (ADCC)
the bound antigen-antibody complex recognized by natural killer cells (Fc tail of the antibody) which release degranulate, granules contain perforins which form pores in the cell that allow entry of water + granzymes + granulysin which together cause apoptosis (no surrounding inflammation)
Non-cytotoxic mechanism - antibody-mediated cellular dysfunction
- Myasthenia gravis -> antibodies specific for the acetylcholine receptor in muscles block the binding of acetylcholine which causes the muscles to not get stimulated and progressively weaken
- Grave’s disease -> antibodies target receptors that stimulate thyroid hormone production causing hyperthyroidism
A _____ Coombs test can be used in type II hypersensitivity reactions to detect antibodies
direct
In type II hypersensitivity reactions, ___ ___ cells recognize the Fc tail of an antibody and release perforins and granzymes, which causes apoptosis
natural killer
The first line of treatment in ABO transfusion reactions is _____ _____ ___ _______
immediately stopping the transfusion
The second step of management in ABO transfusion reactions is _____ _____
vigorous hydration
The best treatment of Goodpasture syndrome are…
corticosteroids and cyclophosphamide
Type II hypersensitivity reactions are also called _____ hypersensitivity due to the antibody-mediated destruction of specific cells
cytotoxic
______ _____ is a type of nephritic syndrome due to type II hypersensitivity
Goodpasture syndrome
A(n) ______ Coombs test can be used in type II hypersensitivity reactions to detect unbound antibodies in the serum
indirect
Reactions due to ___ incompatibility are an example of type II hypersensitivity
ABO
When the antibody disrupts cell function instead of killing the cell, it is called a _____ type II hypersensitivity reaction
non-cytotoxic
Type II hypersensitivity most commonly involves ___ antibodies
IgG
In type II hypersensitivity reactions that cause cellular _____ the cell is opsonized by antibodies, leading to _______ or antibody-dependent cytotoxicity
destruction, phagocytosis
In type II hypersensitivity reactions, B cells produce ___ or ___ antibodies
IgG and IgM
______ ______ anemia is an example of type II hypersensitivity reaction
autoimmune hemolytic
Pathology
- antibody-mediated hypersensitivity reactions, tissue-specific, broad spectrum of disease manifestation
- disorder due to self-reactive B cells that produce antibodies (ie IgM and IgG) which bind antigens on host cells and form antigen-antibody complex at tissue site
Causes
Defective central tolerance -> autoantibodies against intrinsic antigens; extrinsic antigens into normal cell surface alter cell antigenicity
Common reactions
hemolytic disease of the newborn, autoimmune hemolytic anemia, immune thrombocytopenic purpura, bullous pemphigoid, pemphigus vulgaris, rheumatic fever, goodpasture syndrome, guillain-barré syndrome, graves’ disease, myasthenia gravis, pernicious anemia
Types - activation of complement system (IgM/IgG antibody binds fixed antigen on cell)
IgM/IgG antibody binds fixed antigen on cell -> C1 binds Fc portion of IgM/IgG -> classical pathway C2 - C9 cleavage/activation -> C3a - C5a anaphylatoxin production:
- chemoattract and promote degranulation of neutrophils + basophils + mast cells (granules of lysosomal contents of leukocytes fuse and degrade target cell -> cell death; mast cell degranulation contents include histamine -> promote further immune cell response)
- promote macrophage + monocytes + pro-inflammatory cytokine release, IL-1/-6 (ie Goodpasture’s syndrome, antibodies against Type IV collagen in lung + kidney)
Types - activation of complement system (Membrane attack complex (MAC) formation)
C5b-C9 -> insertion into, disruption of cell membrane -> impaired osmotic gradient -> cell lysis (ie ABO mismatch, hyperacute transplantation reaction)
