Immunology-Lymphocytes Flashcards
What are the major components of innate immunity?
Neutrophils, macrophages, monocytes, dendritic cells, NK cells, and complement
What are MHC molecules?
MHC are encoded by HLA genes and present antigen fragments to T cells anf bind TCRs
Overview of MHC I
Loci: HLA-A/B/C
Binding: TCR and CD8
Expressed on all nucleated cells (not on RBCs)
Function: Presents endogenously synthesized antigens (e.g. viral or cytosolic proteins) to CD8+ T cells
Overview of MHC II
Loci: HLA-DR/DP/DQ
Binding: TCR and CD4
Expression: On APCs
Function: Presents exogenously synthesized antigens (e.g. bacteial proteins) to CD4 helper T cells
What is the major association of the A3 HLA subtype?
hemochromatosis
What is the major association of the B27 HLA subtype?
Psoriatic arthritis, Anklyosing spondylitis, arthritis of Inflammatory bowel disease, Reactive arthritis
What is the major association of the DQ2/8 HLA subtype?
Celiac Disease
What is the major association of the DR2 HLA subtype?
MS, Hay fever, SLE, and Goodpasture Syndrome
What is the major association of the DR3 HLA subtype?
DM type I, SLE, Graves disease, Hashimoto Thyroiditis
What is the major association of the DR4 HLA subtype?
Rheumatoid arthritis, DM type I
What is the major association of the DR5 HLA subtype?
Pernicious anemia- vitB12 deificency, hashimoto thyroiditis
How do NK cells work?
They use perforin and granzymes to induce apoptosis of virally ifnected cells and tumor cells (lymphocyte membrer of the innate immune system)
They are induced to kill when exposed to a nonspeciifc activation signal on target cell and/or to an absence of class I MHC on target cell surface. Also kills via antibody-dependnet cell-meidated cytotoxicity (CD16 binds to Fc region of bound Ig, activating the NK cell)
NK cell activity is enhanced by what cytokines?
Enhanced by Il2, Il12, IFN-a, and IFN-B
Describe the development of T cells
T cell percursors are made in the BM and travel to the thymus cortex where they express both CD4 and CD8 molecules. In the cortex, positive selection occurs and T cells expressing TCRs capable of binding surface self-MHC colmecules survive. They then go to the medulla as CD4 or CD*+ T cells where negative selection occurs.
CD4 T cells can then turn into Th1 (via IL12), Th2 (via IL-4), or TH17 cells (via TGF-B and IL-6)
What do Th1 cells do?
Secrete IFN-y and Activates macrohages and cytotoxic T cells
Activated IFN-y and IL-12
Inhibited by IL-4 and IL-10 (from Th2 cells)
What do Th2 cells do?
Secrete IL-4/5/10/13
Recruit eosinophils for parasite defense and promotes IgE production by B cells
Activated by IL-4
Inhibited by IFn-y (Th1 cells)
Macrophage-lymphcyte interaction- macrophages release Il-12, which stimulates T cells to differentiate into Th1 cells. Th1 release IFn-y to stimulate macrophages.
What cytokines do Tregs secrete?
Anti-inflammatory cytokines such as Il-10, TGF-B
How are Tregs ID’d?
By their expression of CD3/4/25 and FOXP3
How are T cells activated?
Dendritic cells sample and process antigens and migrate to draining lymph nodes. The foreign antigen is presented on MHC II and recognized by TCR on Th (CD4+) cells or by MHC I to CD8.
Costimulatory signals occur via interaction of B7 on APCs and CD28 on T cells
Th cell activates and produces cytokines
How are B cells activated?
Acvtivated Th cells and MHC processing and CD40/CD40L binding activates B cells
What is the structure of Abs?
Fab (variable) region consisting of light and heavy chains recognize antigens. the Fc region off IgM and IgG fix complement.
Light chains contribute only to the Fab region while the heavy chains contribute to the Fab and Fc regions
More about the Fab region
Binds antigen and determines the idiotype: i.e. unique antigen-binding pocket (only 1 antigenic specificity expresed per B cell)
More about the Fc region
Constant, complement binding occurs here
Determines the isotype (IgM, IgG, etc.)
How is Ab diversity generated?
Random recombination of the VJ (light-chain) or V(D)J (heavy-chain) genese
Random combination of light chains with heavy chains
Somatic hypermutation following antigen stimulation
Addition of nucleotides to DNA during recombination by terminal deoxynucleotidyl transferase
Describe the basis of immunoglobulin type switching
Mature B cells express IgM and IgG on their surfaces. They may differentiate in germinal centers of lymph nodes by isotype switching (gene rearrangement; mediated by cytokines and CD40L) into plasma cells that secrete IgA, IgE, or IgG
Describe IgG
This is the main Ab in secondary (delayed) response to an antigen.
Most abundant Ab in serum
Fixes complement, crosses the placenta (provides infants with passive immunity), opsonizes bacteria, and neutralizes bacterial toxins and viruses
Describe IgA
Prevents attachment of bacteria and viruses to mucous membranes
does NOT fix complement
Monomar (in circulation) or dimer (when secreted)
Crosses epithelial cells by transcytosis.
Produced in the GI tract and protects against gut infections
released into secretions (tears, saliva, mucus) and breast milk (picks up a secretory component rom epithelial cells before secretion)
Describe IgM
Produced in the primary (immediate) response to an antigen.
Fixes complement but does NOT cross the placenta.
Monomer on B cells and pentamer when secreted
Describe IgE
Binds mast cells and basophils; cross-linls when exposed to allergens, mediating immediate (type I) hypersensitivity through release of inflammatory mediators such as histamine
Lowest conc. in serum
Protects against worms
What are ‘thymus-independent” antigens?
Antigens lacking a peptide component (e.g. LPS from gram-neg bacteria) that CANNOT be presented by MHC to T cells
