Alteration in the immune response Flashcards
3 types of alterations in immune response
Hypersensitivity Reactions Type I Type II Type III Type IV Autoimmune Disorders Immunodeficiency Disorders
IgG
secreted by plasma cells in blood, can cross placenta
IgA
found in secretions (sputum, breast milk, tears). pathogen protection
IgM
attached to surface of B cell or in blood. responsible for early stages of immune response
IgE
parasitic, worm defense. mount allergic rxn
IgD
part of B cell receptor, activates basophils and mast cells
types of hypersensitivity rxns
- immediate hypersensitivity -IgE mediated : allergies or parasitic
- antibody mediated: IgM or IgG, cytotoxic: in blood transfusion rxns + autoimmune anemia
3 immune-complex (Ab-Antigen) mediated: generalized rxn ie rheumatic arthritis and serum sickness (vague presentations)
4: cell-mediated hypersensitivity: i.e. contact dermatitis
type 1 hypersensitivity rxn
Immediate Hypersensitivity: IgE mediated; rapid onset
Sensitization of mast cells with antiG –> IgE antiBs attach to the mast cells
-next exposure the antiG binds to IgE antiB
=Degranulation of the mast cell and mediators released.
- Initial response mediators are:
Mast cells degranulate and preformed mediators
(histamine, acetylcholine, kinins) released
–> vasodilatation, increased permeability, smooth muscle contraction and bronchial constriction (SOB) - Late response: 2 - 8 hours later; same effects but lasts several days
Prostaglandins
Leukotrienes
Cytokines
most important cell types in type 1 hypersensitivity
TH2 (helper T cells) and Mast Cells
vasodilation, smooth muscle constriction and inflammation expanded and how do we counter these?
- Vasodilation- mostly venous precapillary dilation, decrease in preload, decrease in BP, and shock.
- Smooth muscle constriction in bronchial tree (SOB)
- Inflammatory response: recruitment of inflammatory mediators, increase in permeability of vasculature, leaking vessels, fluid collection in the tissues, etc . . .
to counter these problems we need a sympathetic agonist to help: Epinephrine
Beta-2 is a bronchodilator
Alpha-1 is a vasoconstrictor
anaphylactic rxn: what is it? primary and secondary treatment?
Severe rxn to antiG
Life-threatening hypersensitivity rxn: widespread edema, difficulty breathing, and vascular shock secondary to vasodilation
-Reaction depends on level of sensitization
-Primary Treatment: stabilize the airway, vascular access, epinephrine
-Secondary Treatment: solumedrol ( anti-inflamm. steroid), zantac, benadryl + epi pen
local rxn and treatment
AntiG confined to a particular site by virtue of exposure.
Atopic- genetically determined hypersensitivity to common environmental allergens mediated by IgE-mast cell rxn
ex/ Allergic rhinitis, Food allergies
Treatment:
Antihistamines
Corticosteroids
Immunotherapy- allergy shots cause IgG to be produced which bind anitG before it can get to mast cell IgE complex
type 2 hypersensitivity
Anit B (IgG or IgM) mediated AntiB formed on “self” cells or tissue components
- Complement and AntiB-mediated CELL DESTRUCTION
Deletion of cells targeted by Ab by complement system or by Ab-dependent cell-mediate cytotoxicity (ADCC)
Ex: Mismatched blood transfusion - Complement and Antibody-mediated INFLAMMATION
AntiB deposited in cell matrix and basement memb.=activates complement, injury from inflammation
Ex: vascular rejection of organ grafts - AntiB-Mediated CELL DYSFUNCTION
AntiB binds cell receptors= change in cell function
Ex: Grave’s disease- autoantibodies to TSH receptors stimulate thyroxine production
type 3 hypersensitivity
immune complex (AnitB-AntiG) mediated
complement activate neutrophils and start inflammation (C. Cascade stuck at C5a level= chronic inflammation –> cell damage)
Regions: kidney, blood vessels, joint synovial
1. systemic immune complex disorder
–> serum sickness (IgG, IgM, some IgA) deposits into regions. caused by abx, drugs, venom etc
–>urticaria, edema, fever
2. local immune complex rxn
–>arthus rxn: local inflamm. + tissue necrosis from vasculitis. cause: immune complexes
type 4 hypersensitivity
cell mediated (not AnitB)
-cell death and injury in response to chem. agents
1. Direct cell-mediated cytotoxicity
CD8 targets + destroys APCs containing cytopathic or noncytopathic virus
2. delayed- type hypersen. disorder
antiG+APC –> sensitized TH1 : releases inflammation mediators
…then goes to direct cell- mediated (activated TH1/CD8 destroys APCs containing cytopathic or noncytopathic virus
-it takes time (24-72 hours) for T helpers to form T effectors i.e. TB test or allergic contact derm (poison ivy)
Autoimmune disorder + self tolerance
breakdown of system’s ability to distinguish self from nonself
thymus: deletes problem Tcells
bone marrow: takes out problem B cells
hopefully these don’t get into immune system —> if they do peripheral organs of immune system try to fix, if they can’t= autoimmune.
- local or multi-organ
-Mechanism of damage: same as immunity or hypersensitivity rxns, but aimed at “self” markers (now considered antigens)
Self-tolerance: the ability to tolerate your own antigens. The human leukocyte antigens (HLA) coded by the major histocompatibility complex (MHC) genes serve as recognition markers of self for the immune system. HLAs are on most nucleated cells.
mechanisms of autoimmune disease
- Genetic Susceptibility- certain HLA types
- Environmental factors
- -Breakdown of T-cell anergy: lymphocyte is functionally inactivated after Ag encounter, but remains alive for an extended period of time in hyporesponsive state
- -Release of sequestered antigens: any self-antigen released after being isolated during development are regarded as foreign=immune response
- -Molecular mimicry: microbe shares an immunologic epitope w/host
- -Superantigens: staph and strep exotoxins that can short-circuit the normal sequence of events in an immune response
diagnosis of autoimmune disease
- evidence of autoimmune rxn
- determine that findings aren’t from another disorder
- no other possible cause
- basis: clinical findings and serologic testing (bloodtest for antiB levels: test again cell components or tissue antiGs)
treatment of autoimmune disorder
Based upon the: Tissue or organ involved Effector mechanism involved The magnitude and chronicity of the effector process Focus on the underlying mechanism
treat: Corticosteroids and immunosuppressive drugs
Plasma exchange therapy
transplant immunopathology: what is rejection? what are HLAs?
Rejection: recipient’s immune system recognizes the graft (transplanted cells/tissues/organs) as foreign and attacks it
Human leukocyte antigens (HLAs): the cell surface Ags that determine whether the tissues of transplanted organs is recognized as foreign
3 types of tissue grafts
Autologous graft: donor and recipient are same person
Syngeneic graft: donor and recipient are identical twins
Allogeneic: donor and recipient are related or unrelated, but share HLA types
transplant rejection process
involves cell-mediated immunity + circulating antibodies
T LYMPHOCTYES REQUIRED- recognize allogenic (foreign) Ags in the graft in 2 ways…
1. Direct Pathway: T cells of the recipient directly recognize allogeneic MHC molc on the surface of Ag-presenting cells on the graft; CD4+ and CD8+ are involved in this type of rejection and kill the cells in the grafted tissue
- Indirect Pathway: recipient CD4+ T cells recognize donor MHC molc after they have been picked up, processed, and presented by the recipient’s own Ag-presenting cells; activates DTH (delayed-type-hypersens.) pathways of the type IV hypersensitivity reactions; produces Ab against graft alloantigens
3 types of transplant rejection
hyperacute, acute, chronic
hyperacute rejection
occurs immediately after transplant
most common in kidney transplants; produced by existing recipient Ab to graft Ags that initiate a type III, Arthus-type hypersensitivity rxn in the blood vessels of the graft (inflammation and cell death)
