CD4’s effect on other leukocytes
- acts as T helpoer for b cells to make ig
- activates cell mediated immunity (cd8, nk, and macrophages)
- activate effector cells of innate immunity (eosinophils, neutrophils)
general mechanism of cd4 activation
- antigens interact with APC,
- thic complex secretes cytokines
- cd4 t cell binds to antigen mhc complex
- cd4 t cell differentiates into subset
- different effector cells are activated based upon the subset
Th1
- involved in response to intracellular pathogen, virus and bacteria
- secretes IFNgamma and IL2
- activates cd8, nk, and macrophages
- activated effector then go do kill cells that are infected with the virus
Th2
- involved in the response to wormsm and allergens
- IL4 is present early on but we do not know where it comes from
- it stimulates, along with the MHC antigen complex, cd4 t cells to differentiate into Th2
- Th2 releases IL5, IL4 and IL13
- IL5 ativates eosinophils
- IL4 and 13 activate plasma cells which produce IgG4 and IgE
- IgE and eosiniphils are the effectors of the Th2 response
- also involved in asthma (high eosinophils and IgE)
Th17
- responses to fungi and extracellular bacteria
- releases IL17
- this is a proinflammatory response which activates neutrophils and epithelial cells, especially at mucosa surfaces
- also involved in atuo-inflammatory conditions such as rheumatoid arthritis, multiple sclerosis and psoriasis
cross inhibition of subset function
- once a subset is produced, it starts releasing its signature cytokines
- these cytokines inhibit the production of the other cd4 t cell subsets
thymus dependent antigens
-require help from cd4 t helper cells in order for b cells to synthesize antibodies
Th are required for
- formation of germinal center in LN
- generation of long-lived antibody responses after infection or vaccination
interaction of antigen with antigen specific b and t cells in a lymph node
- B cell captures and internalizes antigen via ig
- b cell presents peptide on MHC class 2 to a cd4 cell
- dendritic cell bearing the same peptide activates cd4 with the right TCR in the t cell area of the node
- this
Th-B cooperation in antibody sythesis
- mutual activation of the Th and B cell
- cytokines and cell surface interactions
- Th synthesizes cytokines and b cells make ab
- activation requires the first signal of peptide and mhc 2 binding to TCR then the second signal of costimulator pairs B7 and CD28, CD40 and CD40L
what do the cytokines made by the t cell after activation by a b cell determine?
-the class of ab that the b cell will produce once differentiated
CD40 binding to CD40 ligand is important for what?
-activation od AID which helps in class switch reombination
a defect in class switch recombination results in what and stems from what
- stem from defects in CD40, CD40L, or AID
- this causes hyper IgM syndrome: increased igM, decreases IgG/A/E
thymus independetn antigens and Ab response
- do not require t cell help for b cells to secrete ab’s
- LPS
- capsular polysaccharide: strep pneumoniae and flu B
- IgM predominates, no t cell derived cytokines, no class switch
- no memory, b cells witch make IgM are not memory cells
- hard to make vaccines (however conjugate vaccines linked to proteins allow us to circumvent)
cd8 t cells
- must be activated before they kill their target which is typically a virus infected or tumor cell
- activation separable from killing phase
- several mechanisms to activate
- requires 1st and 2nd signal from APC (usually DC) and cytokines
- most viruses need cd4 t cells to activate cd8 cells, some do not
how does a cd8 kill its target cell?
- interacts with a cell producing its counterpart MHC class 1
- the cd8 then releases granules from the surface of the cell closest to the cell expressing the mhc
- these granules(serine esterases) form a pore in that cell and enter in order to activate apoptosis
- it can also do this through Fas L and Fas R
turning off the t cell response
- induction of cell surface molecules that inhibit the reponse
- this signal is transmitted via the CTLA receptor on the activated t cell
- expression of PD-1 on proliferating t cells and interaction with PDL-1/2 is also inhibitory, this is called t cell exhaustion
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Introduction to the Immune Respose26
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Antibody Structure and Function30
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Antibody genetics13
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B cell development17
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Antigen presentation18
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T cell differentiation19
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T cell activation21
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Cellular cooperation17
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Regulation Tolerance30
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Complement17
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transplantation and tumors22
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Immediate hypersensitivity10
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cytotoxic Reaction11
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Immune Def 116
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Immuno deficiency 216
