long vascular channels in red pulp with “barrel hoop” basement membrane?
sinusoids of spleen
where are t-cells found in spleen?
periarteriolar lymphatic sheath (PALS) within white pulp
Where are B-cells found in spleen?
follicles within white pulp
Where are APCs and specialized B-cells found in spleen?
marginal zone between red and white pulp
What organisms increase susceptibility to encapsulated organisms?
SHiNE SKiS Strep pneumoniae H flu Neisseria meningitidis E Coli Salmonella spp Klebsiella pneumoniae Strep (Group B Streptococci)
site of t-cell differentiation and maturation
thymus
what is thymus derived from?
third pharyngeal pouch.
lymphocytes of mesenchymal origin
T-cells =
B-cells =
t-cells = thymus b-cells = bone marrow
components of innate immunity
neuts macrophages monocytes dendritic cells NK cells
components of adaptive immunity
t-cells
b-cells
circulation ab
mechanism of adaptive immunity
variation
mechanism of innate immunity
germline encoded
resistance of innate immunity
persists through generations
resistance of adaptive immunity
not heritable
which is specific in it’s response to pathogens? innate or adaptive immunity?
adaptive
secreted proteins of innate immunity
lysozyme, complement, c-reactive protein, defensins
secreted proteins of adaptive immunity
immunoglobulins
key features in pathogen recognition of innate immunity
TLRs (LPS and ssRNA)
key features in pathogen recognition of adaptive immunity
memory cells (B and T cells)
MHC I loci
HLA-A
HLA-B
HLA-C
MHC II loci
HLA-DR
HLA-DP
HLA-DQ
MHC I binding
TCR and CD8
MHC II binding
TCR and CD4
MHC I expression
expressed on all nucleated cells (not RBCs)
MHC II expression
expressed on APCs
function of MHC I
present endogenously synthesized antigens (viral proteins) to CD8 cytoxic T cells
function of MHC II
present exogenously synthesized antigens (bacterial proteins) to CD4 helper T cells
MHC I associated proteins
beta 2-microglobulin
MHC II associated proteins
invariant chain
Which HLA subtype is associated with hemachromatosis?
A3
Which HLA subtype is associated with the PAIR acronym?
B27
What is the acronym associated with the B27 HLA subtype?
PAIR Psoriatic arthritis Ankylosing spondylitis arthritis of Inflamatory bowel disease Reactive arthritis
Which HLA subtype is associated with celiac disease?
DQ2/DQ8
Which HLA subtype is associated with multiple sclerosis, hay fever, SLE, Goodpasture syndrome?
DR2
Which HLA subtype is associated with DM1, SLE, Graves dz, Hashimotos thyroiditis
DR3
Which HLA subtype is associated with rheumatoid arthritis and DM1
DR4
Which HLA subtype is associated with pernicious anemia, B12 deficiency, hashimotos?
DR5
There are 4 walls in a room (rheum)
rheumatoid arthritis is associated with DR4
What uses perforin and granzmes to induce apoptosis of virally infected cells and tumor cells.
Natural killer cells
What’s activity is enhanced by IL-2, IL-12, IFN-alpha and IFN- beta?
natural killer cells
What are the major functions of B-cells?
- recognize antigen: undergo somatic hypermutation to optimize antigen specificity
- produce ab: differentiate into plasma cells to secrete specific immunoglobulins
- maintain immunologic memory
CD4 T-cell functions
help B cells make ab and produce cytokines to recruit phagocytes and activate other leukocytes
CD8 T-cell functions
directly kill virus infected cells
Rule of 8 in reference to T-cell functions
MHC II X CD4 = 8
MHC I X CD8 = 8
Helper Th1 cells secrete
IFN-gamma
Helper Th2 cells secrete
IL-4
IL-5
IL-10
IL-13
What do Th1 help T cells do?
activate macrophages and cytotoxic T cells
What do Th2 help T cells do?
Recruit eosinophils for parasite defense and promote IgE production by B cells
What inhibits Th1 and Th2 cells?
IL-4 and IL-10 inhibit Th1
TNF-gamma inhibits Th2
who has CD4, which binds to MHC II on APC?
Helper T-cells
kills virus-infected, neoplastic, and donor graft cells by inducing apoptosis
cytotoxic T cells
Have CD8 which binds to MHC I on virus-infected cells
cytotoxic T cells
help maintain specific immune tolerance by suppressing CD4 and CD8 T-cell effector functions and identified by expression of CD3, CD4, CD25, and FOXP3
regulatory T cells
APCs
B-cells
macrophages
dendritic cells
Fab (variable region on abtibody)
Fragment, antigen binding
Fc region of IgM and IgG fixes complement (CCCC)
Constant Carboxyl terminal Complement binding Carbohydrate side chains - determines isotope (IgM, IgD, etc)
opsonization
antibody promotes phagocytosis
neutralization
antibody prevents bacterial adherence
complement activation
ab activates complement, enhancing opsonization and lysis
What do mature B cells express?
IgM and IgD
isotope switching
gene rearangement mediated by cytokines and CD40L
- switch into plasma cells that secrete IgA IgE or IgG
Most abundant isotope in serum
IgG
- prevents attachment of bacteria and viruses to mucous membranes
- produced in GI tract and protects against gut infections
- has secretory component
IgA
- produced in primary immediate response to an antigen
- does not cross placenta
IgM
- binds mast cells and basophils
- cross links when exposed to ag, mediating immediate type 1 hypersensitivity through release of histamine
IgE
Difference between thymus dependent and independent antigens
- thymus dependent contain protein component and there is class switching and immunologic memory
- independent lack peptide component and cannot be presented by MHC to T cells (need booster/adjuvant)
change in response to inflammation
produced in liver
induced by IL-6
acute phase reactants
coagulation factor that promotes endothelial repair
fibrinogen
prevents release of iron bound by ferritin (anemia of chronic disease)
hepcidin
opsonin: fixes complement and facilitates phagocytosis
- measure of inflammation
C-reactive protein
binds and sequestered iron
ferritin
reduction conserves amino acids for positive reactants
albumin
internalized by macrophages to sequester iron
transferrin
what two acute phase reactants are negative/downregulated?
albumin and transferrin
system of hepatically made proteins that play a role in innate immunity and inflammation
- MAC protects against gram-neg bacteria
complement
activation of complement classic pathway
IgG or IgM mediated (GM makes classic cars)
functions of complement
- C3a, C4a, C5a - anaphylaxis (aaaa)
* C3b - opsinization - binds bacteria (bbb)
complement disorders
C1 esterase inhibitor def: hereditary angioedema
C3 def: increased risk of severe pyogenic sinus and resp tract infections
C5-C9 def: recurrent neisseria
DAF def: causes complement-mediated lysis of RBCs
Hot-T-bone stEAK nemonic for IL’s
IL-1: fever (hot) IL-2: stimulates T-cells IL-3: stimulates bone marrow IL-4: stimulates IgE production IL-5: stimulates IgA production IL-6: stimulates aKute-phase protein
TNF-alpha
mediates septic shock
IL-12
Induces T cells into Th1 cells
IL-8
major chemotactic factor for neutrophils (clean up on isle 8)
INF-gamma
secreted by NK cells and stimulates macrophages to kill phagocytksed pathogens
IL-10
modulates inflammatory response
attenuates immune response (10 and ten in attenuate)
activation of NADPH phagocyte and plays an important role in immune response release of ROS.
respiratory/oxidative burst
deficiency of NADPH oxidase
chronic granulomatous disease
- increased risk of infxn by S. aureus, aspergillus
a part of innate host defense against RNA and DNA viruses
act locally on uninfected cells, priming them for viral defense. Results in apoptosis, disrupting viral amplification
interferon alpha and beta
self surface protein MHC I presents on which cells
all nucleated cells (not mature RBCs)
