exam II Flashcards
type I hypersensitivity: etiology
genetics, environmental exposure
type I sensitization
- enzyme Der P 1 cleaves tight junctions, diffuses into mucosa. Der P 1 taken up by dendritic cells for antigen presentation
- dendritic cell primes T cell in lymph node, Tfh and TH2 induces B-cell class switch to IgE production w/ IL-4
- IgE specific for Der P 1 travels to mucosa, IgE binds to FcER1 receptor on mast cell
type I: FcER1 binding
binding IgE is the tightest of all interactions (irreversible), is found in mast cells, eosinophils, basophils
type I: mast cell activation
IgE binds mast cell in absence of antigen, leads to rapid degranulation
Mast cell activation requires cross linking of FcR-bound IgE to same allergen (multiple IgE bind epitopes)
mast cell soluble products: toxic mediators
histamine and heparin increase vascular permeability, smooth muscle contraction
histamine is an early mediator, binds histamine receptors on vascular endothelium, smooth muscle, epithelium
mast cell soluble products: cytokines
Late mediators, after degranulation
IL-4, IL-13 stimulate and amplify TH2 response
IL-5 induces eosinophil production, activation
mast cell soluble products: lipid mediators
leukotrienes: similar to histamine, more potent
- increase vascular permeability, smooth muscle contraction, mucus secretion
type I: eosinophils
- not tissue resident, circulate in low numbers
- recruited to site or generated
- granules are highly toxic, can damage host, produce cyto/chemokines
type I: basophils
- low numbers in circulation, also recruited
- express CD40L, help activated B cells class switch to IgE, IL-13, activate inactive B cells
RIST
radioimmunosorbent test quantifies total IgE in serum: not for verifying allergen types
RAST
radioallergosorbent test used to ID allergen-specific IgE
type I treatments
epinephrine: vasoconstrictor, bronchodilator
anti-histamine: blocks histamine binding to HI receptors
corticosteroids: general leukocyte inhibitors
type II hypersensitivity: etiology
antibody driven, typically IgG
type II: triggers
haptens: nonimmunogenic small molecules that modify host cell surface proteins
molecular mimicry: AB specifically generated against pathogen antigen, reactive against host antigens
autoimmunity: loss of tolerance to self-antigens
type II: small molecule drugs
ex) penicillin modifies proteins on human RBCs to create foreign epitopes, IgG made against new antigen
Complement-coated penicillin modified erythrocytes are phagocytosed, macrophages present peptides to CD4 T cells to differentiate into Tfh
type II: cytotoxic effector phases
complement fixation, opsonization/phagocytosis, ADCC mediated by NK
type II: non-cytotoxic effector phase
receptor-ligand interference
type III: etiology
- body fails to clear immune complexes, which deposit in vessels and cause inflammation
- antigens present in excess, large antigens w/ multiple epitopes fix complement
type III: effector mechanisms
complement fixation, FcyR mediated binding leads to histamien release and inflammation
type IV etiology
- T cells cause pathology
- contact: haptens, metals modify internal proteins to activate T cells
type IV: effector phase
CD4 Th1, Th17 recognize antigens, release mediators that recruit and activate inflammatory cells
type IV: chemokines function
macrophage recruitment
type IV: IFN-y function
macrophage activation
type IV: TNF-a function
local tissue destruction, increased adhesion molecules on blood vessels
type IV: IL-3 function
monocyte production
autoimmunity
immune reactivity against self-antigens resulting from a break in self-tolerance
autoimmunity: central tolerance breakdown related to T cells
-Autoreactive T cells gain access to immune-privileged sites/cryptic antigens, autoreactive T cells escape
tolerance
immune system ignores or induces tolerogenic response so self-antigens don’t elicit inflammatory response
- central: fine-tuning B, T cell receptors
- peripheral: anergy, Treg suppression, cryptic antigens
autoimmunity: peripheral tolerance breakdown anergy
T and B cells recognize antigen w/o costimulation –> become unresponsibe
autoimmunity: central tolerance breakdown due to genetic defect
Genetic defect: AIRE deficiency causes multi-organ autoimmune condition involving both B and T cells
autoimmunity: peripheral tolerance breakdown immune privilege
barriers to prevent leukocyte entry broken down, inflammation occurs
autoimmunity: peripheral tolerance breakdown Tregs
recognize self-antigen, send signals to suppress T cell responses to same antigen
primary immunodeficiency etiology
inherited or acquired gene defect, can be autosomal or x-linked
primary immunodeficiency: complement defect
- classical pathway: impaired clearance of immune complexes, infection by pyogenic bacteria
- alternative pathway defect: infection by N. gonorrhoeae, N. meningintidis
- Masp-2 deficiency: infection by S. pneumoniae
enumeration: T cells
CD4, CD8, CD3
enumeration: B cells
CD20, Ig+
enumeration: phagocytes
neutrophils
assessment of in vitro functioning: T cells
IL-2 production, antigen-specific stimulation
assessment of in vitro functioning: phagocytes
NBT test for ROS
assessment of in vitro functioning: complement
hemolysis assay
assessment of in vivo functioning: T cells
delayed HS to PPD of tuberculosis
assessment of in vivo functioning: B cells
specific antibody levels
cytotoxic drugs immunodeficiency
- chemotherapy targets rapidly-dividing cells
- restricts stem cells
radiation immunodeficiency
- restricts stem cells, inhibits lymphocyte proliferation
immunosuppressive drugs immunodeficiency
inhibit signaling pathways
tumors immunodeficiency
- disrupt lymphoid tissue interactions
- crowd out development of normal immune response
aging immunodeficiency
- primarily affects T cells
- reduced naive T cell production, reduced phagocyte function
- reduced antibody affinity
infection immunodeficiency
malaria: inhibits dendritic cell function
measles: infects dendritic cells, decreases T cell responsiveness
staphylococcus: TSS leads to T cell exhaustion
HIV: CD4 depletion
immune response to tumors: immunoediting elimination phase
elimination phase: neo-antigens recognized, cells attacked and destroyed
immune response to tumors: immunoediting equilibrium phase
- lymphocytes and IFN-y put selection pressure on tumor cells that survived elimination to contain tumor
- results in genetically unstable mutating tumor cells: mutants w/ altered neoantigens
immune response to tumors: immunoediting escape phase
- tumor cell variants selected in equilibrium phase can grown in intact environment
- breach of immune defenses causes resistance to immune detection, tumor expands
anti-tumor immunity: NK cells
- respond to stressed/abnormal cells
- detect and lyse tumor cells w/ no or low MHC 1
- Have Fc receptors: can kill cells bound to antibody by ADCC
anti-tumor immunity: T cells
- mutated antigen must be processed by protease
- peptide containing mutated AAs bind patient’s MHC I
PD-L1, PD-1 inhibition
CTL not activated, tumor grows
PD-L1, PD-1 blockade
CTL activated, tumor killed
glucocorticosteroids: target, mechanism
- targets innate and adaptive
- steroid binds steroid receptor w/ HSP –> can enter nuclear membrane
- decreases T cell activation, IL-2, neutrophil trafficking, presence of eosinophils, macrophages, DCs
cyclosporin: target, mechanism
- targets calcineurin
- cyclosporin A binds immunophilin, which binds calcineurin instead of calmodulin
- calcineurin doesn’t activate –> can’t dephosphorylate NFAT
rapamycin: target, mechanism
- inhibits AKT/mTOR to decrease T, B cell proliferation and survival
cytotoxic drugs: target, mechanism
- inhibit growing cells
- affects immune system as a whole
- Low WBCs: patient at risk of infection
live attenuated vaccine: advantages
- induces humoral and cell-mediated immunity
- only one dose needed for long-lasting protection
live attenuated vaccine: disadvantages
- pathogen can revert to virulent phenotype
- transmission from person - person
- possible adverse rxns
live attenuated vaccine: methods
- using closely-related pathogens from different animals
- growing pathogen in unnatural host/culture
- administration via unnatural route
- genetic manipulation
inactivated vaccine: methods
- pathogen is killed by exposure to heat, chemicals
inactivated vaccine: advantages
- safe: pathogen can’t replicate
- minimal interference from circulating antibodies
- easy to make
inactivated vaccine: disadvantages
- not as effective as live
- mostly humoral response, antigens not produced in cells
- low memory, antigenically weak, contain adjuvants
- multiple doses needed
subunit vaccines: methods
- antigenic fragments of microbes + adjuvants
subunit vaccines: advantages
- chemically-defined, can’t replicate: no chance of disease
- minimal antibody interference
subunit vaccines: disadvantages
- not as effective as live, mostly humoral response
- titer diminishes overtime
- depends on effective adjuvant
autograft
self graft
isograft
identical twin
allograft
human to human, not identical
xenograft
different species
ABO matching
- lab mixes blood of donor w/ serum of recipient to see if there’s a cross rxn
- binding donor cells, antibodies from recipient serum
hyperacute graft rejection
- from preexisting antibodies
- occurs within hours
- IgM to ABO/other antigens
- IgG against MHC antigens
- antibodies bind endothelial cells in graft, fix complement
acute graft rejection
- days-weeks
- donor tissue is recognized by immune cells, immune response mounted
- mostly T cell response, resembling type IV HS
acute graft rejection: T cells
- CD8 recognize donor MHC I
- CD4 recognize donor MHC II
acute graft rejection: mechanism
- CD4 T cells activated by graft APCs, leading to inflammation, damage
- CD8 T cells recognize graft cells, CTL
- CD4 T recognize graft leading to inflammation, develop alloantibodies
- alloantibodies bind graft, leading to MAC, ADCC
chronic graft rejection
- antibody and T cell mediated
- loss of graft function
- months to years later
tumor evasion
- lack of T cell recognition of tumor leads to failure to produce tumor antigens, MHC mutations
- inhibition of T cell activation
