Exam II Flashcards
Type I Hyper-sensitivity
Allergy and Anaphylaxis
Type II hypersensivitity
antibody-mediated cytotoxicity
Type III Hypersensivitity
Immune complex disease
Type IV Hypersensitivity
Delayed-type hypersensitivity
Definition of Type I Hyper-sensitivity. Note cell types and Ig involved.
Allergy and Anaphylaxis: Rapidly progressing immune rxn thru antigen binding to surface of Ig-E-coated basophils or mast cells
What is atopy?
Tendency to develop allergies. Make IgE in response to allergens (normally made in response to parasites)
Does Th1 or Th2 response play a role in Type I HS? Why?
Th2 is default pathway in absence of inflammation. Allergens don’t elicit inflammatory responses: IgE production is natural outcome
What is the hygiene hypothesis?
D/t decreased exposure to pathogens early in life (which would favor development of Th1-mediated immune responses) Th2-mediated immunity takes over: subsequent production of IgE
Explain Development of Anaphylaxis
See Slides
Histamine effect in allergy/anaphylaxis
Bronchial sm cx and increased vascular permeability. Pre-formed in granules of mast cells / basophils. Short lived effect.
Protease effect in allergy/anaphylaxis
activate matrix metalloproteinases which cleave tissue matrix proteins to cause damage
TNF-alpha effect in allergy/anaphylaxis
Promotes inflammation
Explain the eosinophil chemotactic factor of anaphylaxis
Accumulation of eosinophils locally or in bloodstream (systemic anaphylaxis) : attempt to counteract effects of histamine
Leukotrienes (LTs) in anaphylaxis
Most potent substances known that cause sm cx and increased vascular permeability. Released slower than histamine (made, not pre-formed) and has longer effect.
Role of eosinophils in anaphylaxis
Accumulate in nasal and bronchial mucosa in resp allergies and intestinal mucosa during certain worm infestations: attach to worms and release granules containing hydrolytic enzymes
Late Phase Response
6-8 hrs after immediate rxn thru secretion of prostaglandins, leukotrienes, chemokines, cytokines by mast cells. 2nd phase of sm cx. Sustained edema. Recruitment of eosinophils and Th2 cells. Remodeling of tissue: sm hypertrophy and hyperplasia. May lead to chronic asthma and assoc. airway hyperreactivity
Detail mechanisms of Epi Tx for Anaphylaxis
Epi binds to beta-adrenergic receptors to cause increase in cAMP. This relaxes cx bronchial sm, tightens endothelial cell junctions (stops fluid loss) and stimulates heart. Only Tx that reverses effect of anaphylaxis.
Antihistimine Tx for Anaphylaxis/Allergy
Bind to histamine receptors to block further binding
Cromolyn sodium and/or theophylline Tx for anaphylaxis/Allergy
Block degranulation of mast cells / basophils
Repeated allergen injections as a preventative measure for allergy/anaphylaxis
High levels of IgG blocking antibody intercept allergen before it reaches IgE-coated basophils. Th1 response that downregulates the Th2 response. IgE levels decrease
Omalizumab as Tx for allergy/anaphylaxis
mouse anti-IgE antibody. Binds to IgE to prevent it from binding to receptor on basophils and mast cells.
Define Type II Hypersensitivity
Type II hypersensitivity is cell destruction mediated by a reaction of antibody to a cell surface bound antigen, which can be intrinsic or an exogenous adsorbed antigen.
Extracellular bacteria cause tissue destruction by
inducing inflammation and releasing some toxins
Most effective immunity against extracellular bacteria
Innate immunity:
Phagocytosis
Alternative complement pathway
Main adaptive immunity against extracellular bacteria
Humoral immunity
IgG opsonizes and toxin-specific antibodies neutralize
Septic shock
due to immune response to extracellular bacteria
Macrophages release TNF and IL-1, causes too high of immune response
Superantigens
some bacterial toxins that bind T-cells and MHC molecules on APC regardless of antigenic specificity
Causes activation of many T-cells, lots of cytokines produced, and septic shock-like condition
Disease-causing antibodies from Rheumatic fever
cross-reactive antibodies bind to sarcolemma proteins in heart and cause carditis
Disease-causing antibodies from Poststreptococcal glomerulonephritis
antibodies form immune complexes with bacterial antigens, and lodge in kidney causing nephritis
Intracellular bacteria thrive by
living inside macrophages
Are inaccessible to circulating antibodies
Innate immunity to intracellular bacteria
Mostly ineffective
Macrophages produce IL-12, which activates NK cells to produce IFN-gamma
IFN-gamma fully activates macrophages, and can destroy some of intracellular bacterai
Most effective immunity against intracellular bacteria
Delayed Type Hypersensitivity (Type IV)
TH1 cells release IFN-gamma & activated macrophages may kill bacteria
If bacteria lives, activated macrophages surround microbes and form a granuloma to prevent spread
Extracellular bacteria evade immunity by
Varying surface antigens
Polysaccharide capsules which resist phagocytosis and inhibit alternative pathway complement activation
Intracellular bacteria evade immunity by
Preventing fusion of phagosomes and lysosomes
Scavenge reactive oxygen intermediates
Negative effects of granuloma formation
compromise tissue function - esp. in lungs
innate immunity against virus
Virus infected cell releases Type 1 IFN that upregulates expression of class I MHC and activates NK cells and causes uninfected cells to release enzymes that block viral replication
First line of defense against virally infected cells
NK cells See absence of class I MHC caused by virus
Adaptive immunity important early in virus infection
Humoral immunity - if antibodies are present (vaccine)
Antibodies bind to virus to prevent from binding to host cell, opsonize virus, and activate complement
Adaptive immunity important during established virus infections
CTL’s kill virally infected cells that have virus antigen on class I MHC
Viruses evade immunity by
altering antigens
prevent class I MHC expression (protects against CTLs)
Killing CD4 T cells (HIV)
Main source of innate immunity in fungal infections
Neutrophils through phagocytosis (lysosomal enzymes and reactive oxygen)
Most important adaptive immunity in fungal infections
Th1 mediated immunity
Innate immunity against parasite infections
most parasites have a mechanism to defeat innate immunity
Helminthic infestations activate
IgE and eosinophils during ADCC (Th2 immunity)
Parasites evade immunity by
antigenic variation, acquired resistance to complement, inhibition of host immune responses, antigen shedding
Mechanism of Type II hypersensitivity
Antibody bound to cell activates phagocytosis
Complement and Fc receptor activates leukocytes - inflammation and tissue injury
Hemolytic disease of newborn
Mother makes IgG to Rh antigen expressed by RBC’s of her child
Mother is Rh-neg, baby is Rh-pos
First Rh-pos child stimulates immune response, unaffected
Second Rh-pos fetus RBC’s destroyed by macrophages in spleen and liver after being seen by maternal IgG
Prevention of hemolytic disease of newborn
Anti-Rh antibodies given to mother before she delivers Rh-pos baby
Antibodies bind to fetal cells in mother and remove them, preventing mother from becoming sensitized to Rh-pos RBCs
Non-cytotoxic Type II hypersensitivity reactions
Do not destroy cells, but disrupt normal function
Grave’s disease - antibodies to TSH receptor causes overproduction of thyroid hormones
Myasthenia gravis - antibodies to acetylcholine receptor blocks nerve impulse transmission to muscles
Immune complex disease (Type III hypersensitivity)
antibodies form complex with antigens
Recruits complement and Fc receptors and activates leukocytes
Immune complex disease induced by
Autoimmune disease (SLE or RA), Serum sickness, drug reactions, infectious disease, inhaled allergens
To develop Type III hypersensitivity immune complexes must
be medium-sized
Optimal proportions of antibody and antigen required
Antigen must persist for long periods
Immune complexes are normally cleared from body by
RBC CR1 protein binds to C3b and C4b on immune complexes
Immune complexes shuttled to liver and spleen and removed from RBC by macrophages
Delayed-type Hypersensitivity (Type IV)
Form of cell-mediated immunity that manifests 24-72 hours after exposure to antigen
Mediated by TH1 cells & requires prior sensitization to antigen
Contact dermatitis
Type IV hypersensitivity
Skin exposure to antigen causes delayed inflammatory response
Tuberculin skin reaction
type IV hypersensitivity
injection of PPD skin test presents antigen to memory T cells
Endothelial cells upregulate VCAM-1 to bind memory T helper cell-expressed VLA-4
T cells migrate to skin & interact with antigen-expressing macrophages
Memory T cells activate and secrete IFN-gamma - amplifies reaction
Large number of macrophages activates - tissue damage & red skin
Autologous graft
transplanted from a person to same person
Syngeneic grafts
transplant between two genetically identical people
Allogeneic graft
transplant between two genetically dissimilar people
Xenogeneic graft
transplant between members of two different species
Orthotopic transplant
graft placed in its normal anatomic location
Heterotopic transplant
placed in an anatomically different site
First set rejection
similar to primary immune response
graft rejected in 7-10 days