T and NK Cells Flashcards
Vocab: Antigens
2 kinds
Antibody antigens: all 3D biological molecules
T cell antigens: mostly linear peptides in the context of an MHC molecule
Vocab: Naive Lymphocyte
T or B cell that has not encountered specific antigen and proliferated
Vocab: Memory Lymphocyte
T or B cell that has recognized/encountered it’s antigen and proliferated
Primary Lymphoid System
Thymus and bone marrow where lymphs develop
Secondary Lymphoid System
Lymph nodes, where the lymphs hang out looking for trouble
Spleen
Second largest lymphoid organ, filters anitgens in blood stream
Red pulp: destroy old RBCs
White pulp: contain lymphoid tissue
B and T Cell Functions
B, Th, CTL, Treg, NK
B: neutralize microbe, phagocytosis
Th: activation of macrophage, inflammation, activation of T and B
CTL: killing infected cell
Treg: suppression of immune
NK: killing of infected cell
Goal of Immune Repertoire
Large enough to recognize any pathogen, specific enough to not harm the self
T Cells and Differentiation
Types and markers, TCR info
All T cells: CD3
T cell receptor (TCR) complex: recognizes specific peptide antigen in the context of an MHC molecule, all have CD3
Helper T: CD4+
Cytotoxic T: CD8+
TCR Chains and Formation
Alpha: V+J+C
Beta: V+D+J+C
Rearranged DNA from germline DNA
Where Do Naive T Cells Develop?
Thymus
T Cell Selection Process
positive and negative
- All thymocytes express CD4+8
- Positive selection: exposed to MHC molecules. If it engages with MHC Class I, then turns into CD8. If engages with MHC Class II, turns into CD4. If no engagement, apoptosis
- Negative slection: MHC with self peptide, if reacts to it then apoptosis, if not then it lives
Less than 5% of thymocytes leave thymus as naive T cells
Two Main Types of T Cells
And their functions
- CD4: helper, 2/3 of peripheral t cells, recognize antigen and MHC II proteins, produce cytokines to help direct immune response
- CD8: cytotixic, 1/3 of t cells, recognize antigen and **MHC I **proteins, kill virally infected cells
What Induces T Cell Proliferation?
IL-2
T Cell: Co Stimulation
Requires: activated APC
- APC increased expression of costimulators and secretion of cytokines
If APC is inactivated, T cell has no response
Lack of co stimulation: T cell does not fully activate, causes anergy
Types of T Cell Connections
Importance of CD28
Anergy/tolerance: MHC and TCR bind with CD8/4, but CD28 doesn’t bind
Nothing happens: self cell with CD28
Activation/expansion: APC with MHC binds to TCR, CD28 binds to self cell marker, CD4/8 also bound
Inactivation/suppression: CTLA-4 bound to self cell, MHC, TCR, 4/8 all bound
How CD8 T Cells Kill: Cytotoxic
MHC I peptide, costimulatory molecules, cytotoxic T cell activated
Perforin: makes a pore in the cell
Granzyme: passes through pore and induces apoptosis
Also fas/fas ligand which also causes apoptosis
Types of Th Cells
3 of them
Th1: makes interferon gamma IFN-y, and tumor necrosis factor-beta TNF-b, protects against intracellular pathogens
Th2: produces interleukins, helps B cells produce antibodies against extracellular pathogens
Treg: CD4 and CD25, suppress immune response by making transforming growth factor B and IL-10, expresses CD25 and CTLA-4
Difference Between Effector and Memory T Cells
And why?
Long process to prepare naive cell, but lots of energy consumed to keep the matura T cells activated
Memory cells: just remembers past infection, lower activation threshold, lasts a long time
Effector cells: activated and ready to respond
Natural Killer Cells: Function
Kills target cells without prior exposure
- Produces IFN-y
- Involved in early infection
- FasL and perforin granzyme methods of killing
Natural Killer Cells: Stimulation and Inhibition
Stimulation: exposure to IL-12, IFN-y, and IFN-b, antibody-coated cells through antibody-dependent cell cytotoxicity (ADCC)
Inhibition: recognizing MHC I, doesn’t attack healthy self cells
Natural Killer Cells: Importance of MHC Proteins
- In diseased cells, lose the ability to make MHC
- NK cells triggered by the lack of MHC
Natural Killer Cells: Preventing the Killing
And virus process?
Inhibitory receptor: KIR
Viruses: down regulate MHC I on host cell to hide from phagocytes and T cells, but NK is stimulated by lack of MHC so it ends up attacking it