General Immuno Flashcards
Location of T cells in the sinusoids of the spleen.
Scattered in the White Pulp
Location of B cells in the sinusoids of the spleen.
Germinal Centers in the White Pulp
4 major infectious organisms more common with asplenia
Encapsulated organisms (lower IgM means no C3b production) Salmonella Strep pneumo H. flu Neisseria m.
What branch of immunity is complement a part of?
Innate
What are HLA-A, HLA-B, and HLA-C?
MHC I receptors
- they bind to TCR with co receptor CD 8 on T cells
- present on all nucleated cells
What are HLA-DR, HLA-DP, HLA-DQ?
MHC II receptors
- bind TCR and co-receptor CD4 on T cells
- present on cells that serve as APCs
What is HLA-A3 associated with?
Hemochromatosis
What is HLA-B27 associated with?
Psoriasis, Ankylosing Spondylitis, IBD, Reiters Syndrome
What is HLA-B8 associated with?
Graves Disease
What is HLA-DR2 associated with?
MS, SLE, hay fever, Goodpastures
What is HLA-DR3 associated with?
DM type 1
What is HLA-DR4 associated with?
RA and DM type 1
Where do positive and negative selection of T cells occur in the thymus?
Positive: cortex, T cells must have TCR that bind MHC
Negative: medulla, T cells that have TCR that bind self antigens are eliminated
Mechanism of CD4 cell activation
- APC “eats” foreign material, digests it, puts it on MHC II
- MHC II recognized by TCR on CD4 on helper T cells
- Co-signal of B7 (on APC) and CD28 (on T cell) must also bind
- CD4 cell produces cytokines (IL-2 ) to activate CD8 cells
2 Mechanisms of CD8 activation
- Cell infected by viral or bacterial pathogen presents material on MHC I
- MHC I binds TCR (along with CD8) on cytotoxic T cells
Another mechanism is IL-2 released from CD4 T cells binds the IL-2 receptor on CD8 T cells to activate them.
Mechanism of B cell activation
- CD4 T cell releases IL-4, IL-5 and IL-6 to induce B cell differentiation and produce Abs
- CD40 (B cells) binds CD40L (T cell) as a Co-stimulation
Difference between Th1 and Th2 CD4 cells
Th1
- CMI
- secretes IL-2, INF-gamma
- inhibited by IL-10
Th2
- humoral immunity
- secretes IL-4, IL-5, IL-10
- inhibited by INF-gamma
Portion of which two Abs induce classic complement pathway?
Fc portion of IgM and IgG
Abs on the surface of Mature B cells
IgM and IgD
Ab that crosses the placenta to give immunity to neonates
IgG
Ab passing thru breast milk
IgA
Ab that forms a pentamer in circulation
IgM
Ab that is used in parasite infections and allergies
IgE
Complement protein that serves for opsonization
C3b
Complement proteins that serve in anaphylaxis
C3a and C5a
Complement protein that serves in neutrophil chemotaxis
C5a
Complement protein that functions to clear immune complexes
C3b
Condition and contraindicated drugs in C1 esterase inhibitor deficiency
Hereditary angioedema
-no ACE-Is
2 pyrogenic cytokines secreted by macrophages
IL-1
IL-6
Chemotactic cytokine secreted by macrophages
IL-8
Cytokine secreted by macrophages that induces Th1 formation and activates NK cells
IL-12
Cytokine secreted by macrophages that mediates septic shock
TNF-alpha
Cytokine secreted by all T cells that induces bone marrow growth and differentiation
IL-3
2 mediators from Th1 cells and the functions
IL-2: growth and differentiation of cytotoxic T cells
INF-gamma: activates macrophages, suppresses Th2 cells
4 mediators from Th2 cells and the functions
IL-4: induces IgE production in B cells
IL-5: induces IgA production in B cells
IL-6: pyrogen
IL-10: inhibits inflammation, suppresses Th1 formation
Function of INF-alpha and beta
Inhibit viral protein synthesis
Function of INF-gamma
induces MHC I and II expression
B cell receptor that binds EBV
CD21
Unique receptor on NK cells
CD56
Mechanism of Superantigens causing shock
Ag facilitates a very strong binding “outside the normal Ag site” of the TCR (w/ CD4) and MHCII. Causing a prolonged binding which induces release of:
IL-1, IL-6, and TNF-alpha from macrophages
Mechanism of LPS endotoxin causing shock
LPS binds CD14 on macrophages induces IL-1, IL6, and TNF-alpha release
Mechanism of passive immunity and a big example
Receive pre-formed Abs
- IgA in breast milk
- rapid acting but not long lasting
Mechanism of active immunity
Actual exposure to foreign antigens causes the body to slowly produce natural Abs to the specific Ag
Mechanism of Type I HS reaction
Allergen stimulates IL-4 release from Th2 cells. Induces B cells to make IgE.
- Fc portion of IgE binds to mast cells and basophils
- second exposure causes mast cell degranulation
Antibodies involved in Type II HS reactions
IgM and IgG
Antibody involved in Type III HS reactions
IgG
-binds and Ag which activates complement (3 things in Type III)
What are 4 general categories of Type IV HS reactions?
T lymphocytes
Transplants
Tuberculosis skin test
Touching (contact dermatitis)
Anti dsDNA Abs
SLE
Antimitochondrial Abs
Primary biliary cirrhosis
Anticentromere Abs
Scleroderma CREST
Anti-desmoglein
Penphigus Vulgaris
Anti-Ro
Sjogren Syndrome (also Anti-SS-A)
c-ANCA
Wegener Granulomatosis
Anti-IgG
RA (anti Rheumatoid factor)
Anti-histone
Drug Induced Lupus
Anti-topoisomerase I
Scleroderma (diffuse)
Anti-basement membrane
Goodpasture Syndrome
Antimicrosomal or Antithryoglobulin
Hashimotos
Anti-La
Sjogren Syndrome (also Anti-SS-B)
anti-Smith Abs
SLE
What is the general rule about T cells deficiency and B cell deficiency
T cell def. produce more fungal and viral infections
B cell def. produce more recurrent bacterial infections
Patient presents with recurrent bacterial infections. What is the gene mutated in this immunodeficiency?
Bruton Agammagobulinemia
- Brutons Tyrosine Kinase
- needed for B cell maturation
Patient presents with severe pyrogenic infection early in life.
Hyper-IgM Syndrome
- Defective CD40L (Th2) or CD40 (B cells)
- receptors needed for class switching
Young patient presents with tetany, recurrent fungal infections, and great vessel defects. What is the embryology behind this condition?
DiGeorge Syndrome (CATCH-22)
- mutation on chromosome 22q11
- failure of the 3rd and 4th pharyngeal pouches
- Cardiac Abnormalities (T of F)
- Abnormal Facies
- Thymic Aplasia
- Cleft Palate
- Hypocalcemia (due to low PTH and no Parathyroids)
Patient presents with recurrent staph infections, also has his baby teeth at 14 years of age and eczema.
Hyper IgE syndrome (Job Syndrome)
-Th cells fail to secrete IFN-gamma for neutrophil chemotaxis
Patient presents early in life with recurrent viral, bacterial, fungal, and protozoal infecitons. What is the mechanism for this condition?
SCID
- defective IL-2 receptor and/or adenosine de-aminase deficiency (can’t produe MHC II)
- inability to produce B and T cells
Patient presents with recurrent mucosal infections, spider angiomas, and difficulty walking.
Ataxia Telangeictasia
-IgA deficiency
Patient presents with thrombocytopenic purpura, recurrent infections, and eczema.
Wiskott Aldrich Syndrome
-low IgM
Patient presents with recurrent bacterial infections without pus formation. Delayed umbilical cord separation.
Leukocyte Adhesion Deficiency
-defect in integrins that bind CD18
Nitroblue tetrazolium dye doesn’t turn blue
Chronic Granulomatous Disease
- defect in NADPH oxidase
- no ROS produced to fight bacteria
- catalase positive organisms
What is a syngeneic graft?
Graft from identical twin
Mechanism of Hyperacute graft rejection
Type II HS reaction of preformed Abs
-cytotoxic, occlusion of graft vessels and ischemia
Mechanism of Graft vs. Host disease
Type IV
-graft from immunocompetent patient given to IC host and T cells attack host
MOA of cyclosporine
Prevents calcineurin formation in T cells. This is a molecular signaling molecule needed for IL-2 production
-used for grafts and gout
