Immunology 3 4 - Complement, T cell, etc Flashcards
4 methods for AB effector mechanisms
B cell receptor; Simple binding; Cell-surface binding via the Fc region: Opsonisation, NK cell ADCC and mast cell degranulation; Complement activation
Describe B cell receptor AB mechanism
AB on surface of B cells act as antigen receptors, internalize antigen. Binding and cross-linking of the surface antibodies signal B cell, and internalized antigen is processed and presented to a helper T cell, which in turn further activates the antigen-presenting B cell.
Describe the Simple Binding AB mechanism
What are the types of Cell-surface binding via the Fc region? Describe the basics a bit
Some cell types have Fc receptors so they may bind ABs in solution. When the AB binds an antigen, the cell bound to the Fc region can react. (note: can have many different ABs on one cell). This includes mast cells and basophils; macrophages and granulocytes.
Describe the mechanism of AB opsonization
AB binds to pathogen. Phagocytes come bind to it via Fc receptors, stabilizes and increases phagocytosis. (note: opsonization can also happen with complement parts, but this requires complement receptors)
Describe ADCC
NK cells bind to Fc of ABs ALREADY bound to pathogen. Depends on avidity (overall strength) of interaction. Results in ADCC (AB dependent Cell-mediated Cytotoxicity)
Describe Mast cell degranulation
Mast cells have high affinity for IgE, so they grab them out of solution, When the IgE bind antigen and cross link (ie two different ABs bind same antigen), the mast cell releases large amounts of histamine
Describe the mechanism of compliment
Basically, when it is activated, some things bind to cells as opsonin and some float away and stimulate inflammation and chemotaxis. Some parts also lead to the membrane attack complex.
Describe briefly the classical, alternate and lectin pathways
Classical is activated by AB/antigen complexes. Alternate constantly activated and covers host cells and pathogens, but host cells have regulatory proteins on surface to prevent its action. Lectin: binding of microbe polysacc to circulating lectins. Lectins are structurally similar to Clq, so it triggers complement system. No AB, rest of pathway is same as classical
What is cleaved when C3, C4, etc split?
Cleaves a thioester bond, then it can bind to something else. C3b binds to cell, other factors, then activates.
Compare the different AB and their relative function with complement
Picture
T cell receptor TCR
Like an AB but only one binding site. One light and one heavy chain. Specific for the antigen peptide and the MHC protein
CD3
Necessary for TCR to work, and always associated with it. It is made of gamma, delta and epsilon chains (one each). CD3 is responsible for signalling inside the T cell.
T cell maturation (early)
Develop receptors, then go through self/non-self selection
Pairs which stabilize interaction for initial activation of naive T cell (signal and co-signals)
Listed T cell protein then target or APC. TCR/MHCI + peptide; CD8/MHCI; CD4/MHCII; CD28/B7; CD2/LFA-3; LFA-1/ICAM-1; CD40L/CD40 (APC only)
What happens when naive T cell is triggered?
Release IL-2 autocrine, then become several cell types: Th for AB production, Th for delayed type hypersensitivity (for activating macrophages), Th for allergic/parasitic response, Th for T cytotoxic response, Tc cells, and memory T cells
What happens inside T cell when activated?
Cascade of signals, lots of phosphorylation leading to transcription for cytokines etc
Cyclosporin A and FK504
Immunosuppressive drug which targets calcineurin which is a phosphatase in the T cell. Blocking it stops the T cell from activating. FK504 is something similar.
How is naive Th cell activated
First get activated in lymph node when interact with dendritic cell and start to differentiate, but require another stimulus from MHC class II expressing APCs, including dendritic cells, macrophages, or B cells
Mutual stimulation b/w Th cell and B cell?
B cell ingests and displays antigen, matching Th cell binds via TCR/CD3 (Th signal 1), CD28/B7 (Th signal 2), then Th cell produces more CD40L to stimulate B cell more. B cell makes cytokine receptors, which can influence class switching and affinity maturation
Affinity maturation of B cell
Proliferates, generating mutations in variable regions of AB. Weak affinity die, good ones continue and dominate the response. Memory cells persist after
B cell memory
There are more B cells specific to that antigen, they are the more specific ones, and the class switch has already occurred. All of these contribute to more effective response next time.
T dependent vs independent response
T dep requires B cell to interact w/ Th cell to get going. T indepe. B cell just binds to a polysaccharide or something like that, No class switching or affinity maturation. Insert pic
