Immunology review and Hypersensitivity reactions Flashcards
Humoral immunity
Protects against extracellular microbes and toxins.
Part of adaptive immune system.
Intracellular immunity
Protects against intracellular microbes and tumor cells.
Part of adaptive immune system.
Generative lymphoid organs (primary or central)
sites where T and B lymphocytes mature and become competent to respond to antigens (thymus for T lymphocytes, bone marrow for B lymphocytes)
Peripheral lymphoid organs (secondary)
Sites where the adaptive immune response is initiated (lymph nodes, spleen, mucosal and cutaneous lymphoid tissues (GI tract, respiratory tract, skin).
Reactive follicular hyperplasia
- Germinal center develops in follicle and becomes hyperplastic
- Occurs when B lymphocytes respond to an antigen.
MHC function
The physiologic function of MHC molecules is to display peptide fragments of proteins for recognition by antigen specific T cells.
MHC gene location
In humans the MHC complex genes are found on chromosome 6 and are also known as the human leukocyte antigen (HLA) complex as they were initially detected on leukocytes.
Where are MHC gene products found?
All mature cells except RBCs
Class I MHC molecules
Coded by HLA-A, HLA-B, and HLA-C genes; display antigens that are recognized by CD8+ T-lymphocytes and NK cells
Class II MHC molecules
Coded by HLA-DP, HLA-DQ, and HLA-DR genes; display antigens that are recognized by CD4+ T lymphocytes
Uses of HLA testing
- Can be used to determine disease risk
- Used in transplantation work-up
Light chain restriction
Kappa or Lamda typein B cells. Ig light chian expressed by neoplastic, monoclonal B cell population.
Ways to detect light chain restriction
- Flow cytometry
- Serum protein electrophoresis with immunofixation electrophoresis
- Kappa and lamda in situ hybridization study
Flow cytometry
-performed on fresh and unfixed tissue, blood, or body fluids.
Can exogenous or endogenous self-antigens elicit a hypersensitivity reaction?
Both
What usually causes a hypersensitivity reaction
Imbalance between the effector mechanisms of immune responses and the control mechanisms that serve to normally limit such responses. Often associated w/inheritance of particular susceptibility genes (HLA an non-HLA genes)
What is the problem with hypersensitivity?
The reactions are poorly controlled, excessive, or misdirected.
Immediate (Type 1) hypersensitivity reaction
- IgE mediated activation of mast cells with degranulation and release of mast cell contents.
- first step: sensitization
- repeat exposure causes mast cell degranulation
- Late phase reaction occurs when activated eosinophils secrete major basic protein and eosinophil cationic protein (toxic to epithelial cells) and activate mast cells to release mediators
Antibody-mediated (type II) hypersensitivity
-Caused by Ab that react with normal or altered cell surface antigens in the extracellular matrix
Atopy
Predisposition to develop immediate hypersensitivity reactions
Hygiene hypothesis
Postulation that improved hygiene has diminished exposure to microbial antigens in early life that “educate” the immune system, setting stage for pathologic allergic responses later in life.
Goodpasture syndrome
Circulating autoantibodies to antigens intrinsic to the glomerular basement membrane results in antibody mediated injury. Resulting anti-GBM immune complexes can be visualized with immunoflourescence microscopy as a linear pattern of deposition.
Pemphigus vulgaris
Due to antibodies directed against desmogleins 1 and 3 (found in the desmosome)
Immune complex mediated hypersensitivity (type 3) Steps
Immune complex formation
Immune complex deposition
Immune complex-mediated inflammation and tissue injury
T cell mediated (Type IV) hypersensitivity
Caused by inflammation resulting from cytokines produced by CD4_ T lymphocytes and cell killing by CD8+ lymphocytes. Sensitized to exogenous or endogenous antigens
2 mechanisms of type IV hypersensitivity
CD4+ T cell mediated inflammation. CD8+ T cell mediated immunity.
CD4+ T cell-mediated inflammation
Response to repeat exposure of antigen, CD4+ cells secrete cytoines and cause recruitment and activation of macrophages and neutrophils causing an inflammatory response that can cause tissue injury
Example of CD4+ T cell-mediated inflammation
Delayed-type hypersensitivity reaction. (Tissue reaction to antigens given to immune individuals)
CD8+ T cell mediated immunity
CD8+ cytotoxic T cells kill antigen expressing target cells
Granulomatous Inflammaiton
Distinctive patern of chronic inflammation. Usually results from a strong activation of T lymphocytes, leading to activated macrophages and causing tissue injury
Granuloma
Focus of chronic inflammation consisting of microscopic aggregation of macrophages transformed into epithelial-like cells (histiocytes).
What can histiocytes fuse to form?
Multi-nucleated giant cells
What are granuloms the result of?
Immune reaction or a reaction to a foreign material
Foreign body granulomas
See foreign material within histiocytes/giant cells.
Caseating granulomas
Induce cell-mediated immune response w/central necrosis. Usually associated with infection
