Immune responses Flashcards
what are acute phase reactants
factors whose serum concentrations change significantly in response to inflammation
where are acute phase reactants produced and what cytokines induce their modulation
produced in the liver; upregulated by IL-1, IL-6, TNF-alpha and IFN-gamma
name five acute phase reactants that are upregulated in response to inflammation
serum amyloid A, CRP, ferritin, fibrinogen, hepcidin
what does C-reactive protein do
CRP is an opsonin; it also fixes complement and facilitates phagocytosis
what does ferritin do
binds and sequesters iron to hide it from microbes
what lab value does fibrinogen correlate with
erythrocyte sedimentation rate
what does hepcidin do
prevents release of iron bound by ferritin
what acute phase reactants are downregulated during inflammation
- albumin (downregulated to conserve amino acids for other acute phase reactants
- transferrin (internalized by macrophages to sequester iron)
which immunoglobulins activate the classic pathway?
alternative pathway?
lectin pathway?
IgG and IgM activate the classic pathway
microbial surface molecules activate the alternative pathway
microbial mannose or other surface sugars activate the lectin pathway
what role does C3b play
opsonization
what three complement molecules mediate anaphylaxis
C3a, C4a, and C5a (C5a is also a chemoattractant)
what complement molecules are needed for formation of the MAC
C5b-C9
what is the role of C3b
opsonization and clearing immune complexes
what do DAF (decy accelerating factor) and C1 esterase inhibitor do
DAF and C1 esterase inhibitor help prevent complement activation on self cells
what disease does C1 esterase cause? and what medication is contraindicated for these patients?
angioedema;
ACE inhibitors are contraindicated
what conditions are C3 deficient patients predisposed to?
severe sinus and respiratory tract infections, as well as type III hypersensitivity rxns (immune complex)
C5-9 deficiencies predispose to what condition
Neiserria bacteremia
what conditions does DAF deficiency predispose to
complement-mediated hemolysis and paroxysmal nocturnal hemoglobinuria
what does IL-1 do
pyrogen
activates osteoclasts
stimulates endothelium to produce adhesion factors
stimulates chemokine secretion to recruit leukocytes
which cytokines are secreted by macrophages
IL-1, IL-6, IL-8, IL-12, TNF-alpha
which cytokines are secreted by all T cells
IL-2, IL-3
what’s the mnemonic for IL-1 through IL-6 main functions
Hot T-Bone stEAK:
1- hot (pyrogen), 2- T cell stimulation, 3-bone marrow stimulation, 4-IgE production, 5-IgA production, 6-stimulates aKute phase protein production
what does IL-8 do
chemotaxis for neutrophils
what does IL-12 do
stimulates differentiation of T cells to Th1; activates NK cells
what are the four main function of TNF-alpha
- mediates septic shock
- activates endothelium
- leukocyte recruitment
- vascular leak
what does GM-CSF do and what interleukin shares a similar function
Granulocyte Macrophage- Colony Stimulating Factor promotes growth and differentiation of white blood cells
IL-3 shares this same function
how does interferon gamma work
has antiviral and antitumor properties
promotes MHC expression and antigen presenting
activates NK cells to kill viral-infected cells
what else does IL-5 do besides promote IgA class switching
promotes differentiation of B cells and eosinophils
what does IL-4 do besides promoting class switching to IgG and IgE
promotes differentiation to Th2 cells, promotes growth of B cells
what two cytokines play a big role in downregulating the inflammatory response
IL-10 and TNF-beta
what are interferons
glycoproteins produced by virally infected cells that prime adjacent cells to be prepared to viral defense
what are the two processes that interferons, produced in response to viral dsRNA, activate in order to induce apoptosis
RNAase L (degredation of viral and host RNA)
Protein kinase (degredation of viral and host protein)
what are the T cell surface proteins
TCR, CD3, CD28
what two cell surface proteins do T helper cells specifically have
CD4, CD40 ligand
what are the B cell surface proteins
Ig, CD19, CD20, CD21 (EBV receptor), CD40, MHC II, B7
what are the macrophage surface proteins
CD14, CD40, MHCII, B7
Fc and C3b receptors (for enhancing phagocytosis)
what are the NK cell surface proteins
CD16 (binds Fc portion of IgG)
CD56 (a unique NK cell marker)
when does anergy occur
T cells become unreactive to self-antigens in the absence of costimulation
B cells can also experience anergy, but it’s not as complete as in T cells
how do superantigens work
superantigens bind the beta region of the TCR and cross-link it to MHC II on APC leading to T cell release of cytokines
name some classic examples of antigenic variation
influenza (reassorment)
salmonella (2 flagellar variants)
gonorrhea (variable pilus protein)
trypanosomes (programmed rearrangement)
for what infections are preformed antibodies often given to protect the patient post-exposure
tetanus, botulinum, rabies, HBV
what kind of immunity does a live attenuated vaccine induce
cellular immunity; strong, often lifelong immunity
name some live attenuated vaccines
Sabin polio, varicella, intranasal influenza, MMR, yellow fever
what kind of immunity does inactivated or killed vaccines produce
humoral immunity
name some inactivated or killed vaccines
cholera, HAV, Salk polio, influenza injection, rabies
what cytokine mediates type I hypersensitivity and how
IgE; binds free antigen triggering histamine to produce anaphylaxis
what cytokines mediate type II hypersensitivity and how
IgG and IgM;
via opsonization, complement activation (along with MACs) and complement-mediated lysis, antibody-mediated destruction via NK cells or macrophages
for which type of hypersensitivity would you expect a positive Coomb’s test (either direct or indirect)
type II (cytotoxic) hypersensitivity
what happens in a type III hypersensitivity reaction
serum sickness; immune complex form and deposit in membranes where they fix complement leading to tissue damage
what is the Arthus reaction
a local, subacute type III hypersensitivity reaction usually seen in experimental settings (a classic example is swelling and inflammation following tetanus vaccine)
what is type IV hypersensitivity
delayed, T-cell mediated immune response (no antibodies involved) in which the correct sensitized T cell binds the antigen and releases lymphokines to activate macrophages
is type IV hypersensitivity transferable via serum
no; there are no antibodies involved
name some type IV hypersensitivity reactions
PPD test, contact dermatitis, transplant rejection (graft vs. host disease), Guillain-Barre, Multiple sclerosis
name some type III hypersensitivity reactions
Lupus, polyarteritis nodosa, post-streptococcal glomerulonephritis, serum sickness, Arthus reaction
name some type II hypersensitivity reactions
autoimmune hemolytic anemia, Goodpasture’s, pernicious anemia, ITP, erythroblastosis fetalis (hemolytic disease of the newborn), acute transfusion reactions, rheumatic fever, bullous pemphigoid, pemphigus vulgaris
what are some common clinical manifestations of type I hypersensitivity reactions
allergic rhinitis/ hay ever, eczema, hives, asthma
what is the clinical presentation of anaphylactic reaction
hypotension/ shock, hives, bronchospasm, dyspnea / respiratory arrest
what’s the difference between targets of febrile nonhemolytic and acute hemolytic transfusion reactions
febrile nonhemolytic: targets are HLA antigens and leukocytes
acute hemolytic: RBC antigens (ABO incompatibility)
name the disorder associated with ACh receptor auto-antibodies
myasthenia gravis
name the auto-antibody associated with Goodpasture’s syndrome
anti-basement membrane antibodies
what antibodies are associated with lupus anticoagulant syndrome
antiphospholipid antibodies
what antibodies are associated with limited scleroderma (CREST syndrome)
anti-centromere antibodies
what does the acronym CREST denote
calcinosis, Raynaud’s phenomenon, esophageal dysmotility, sclerodactyly (tickening and tightening of the skin in localized regions leading to ulcers), telangectasias
antidesmoglein antibodies are associated with what condition
pemphigus vulgaris
what antibodies are associated with SLE
antinuclear antibodies, anti-dsDNA antibodies, anti-Smith antibodies, antihistone antibodies (drug-induced SLE), anti-cardiolipin antibodies
anti-glutamate decarboxylase antibodies are associated with what condition
type 1 diabetes mellitus
what antibodies are associated with bullous pemphigoid and what does the molecule targeted normally do
anti-hemidesmosome;
hemidesmosome normally anchors the epithelial cell to the basement membrane by connecting the keratin in basal cells to BM
what antibodies are associated with polymyositis and dermatomyositis
anti-Jo 1, anti-SRP (signal recognition particle), anti-Mi-2
what condition is caused by anti-microsomal and antithyroglobulin antibodies
Hashimoto’s thyroiditis
what antibodies cause primary biliary cirrhosis
antimitochondrial antibodies
what condition is associated with anti-Scl-70 (anti-DNA topoisomerase I)
scleroderma (diffuse)
what do anti-smooth muscle antibodies cause
autoimmune hepatitis
what antibodies are associated with Sjogren’s syndrome
anti-SSA (anti-Ro), anti-SSB (anti-La)
what antibodies is associated with Grave’s disease
anti-TSH receptor
what condition is associated with anti-U1 RNP (ribonucleoprotein)
mixed connective tissue disease
what disease is c-ANCA (PR3-ANCA) positive
granulomatosis with polyangitis (Wegner’s)
what disease is p-ANCA (MPO-ANCA) positive
microscopic polyangitis and Churg-Strauss syndrome
what antibodies are associated with Celiac disease
IgA antiendomysial, IgA anti-tissue transglutaminase
what antibodies are associated with rheumatoid arthritis
rheumatoid factor (commonly IgM antibodies that are specific to IgG Fc region) anti-CCP (citrullinated protein)
what kind of bacterial infection are you most susceptible to if you have no T cells
sepsis
what kind of bacterial infection are you most susceptible to if you have no B cells
encapsulated bacteria (SHiNE SKiS): strep pneumo, H. flu, Neisseria meningiditis, E. coli, Salmonella, Klebsiella, GBS
what bacterial infections are you most susceptible to if you have no granulocytes
Staph, Burkholderia cepacia, Serratia, Nocardia
what bacterial infection are you susceptible to if you have no complement
Neisseria (due to no membrane attack complexes)
what viral infections are you most susceptible to if you have no T cells
CMV, EBV, JCV, VZV, chronic infections with respiratory and GI viruses
what viral infections are you most susceptible to if you have no B cells
enteroviral encephalitis, poliovirus (live vaccine contraindicated)
what fungi are you most susceptible to if you have no T cell
Candida and PCP
what parasites are you most susceptible to if you have no B cells
GI giardiasis (no IgA)
what fungi are you most susceptible to if you have no granulocytes
Aspergillus and Candida
________ deficiencies cause more recurrent bacterial infections whereas ___________ deficiencies cause more fungal/ parasite infections
B-cell deficiences cause more recurrent bacterial infections whereas T cell deficiencies cause more fungal/ parasite infections
