L08 T helper and Cytotoxin Cells Flashcards
T helper 1 cells
Derived from Th0 by IL-12 and IFNy
- produce IL-2 and IFNy
Orchestrate a cell mediated immune response
Orchestrate a cell mediated immune response :
- up regulate NK cells
- activate Cytotoxic T cells
- activate Macrophages
- up regulate Th1
-B cells switch to IgG3
T helper 2 cells
Derived from Th0 by IL-4
-produce IL-4 and IL-5
Orchestrate humoral immune response
Orchestrate humoral immune response:
-Influences Ig isotopes to IgG1, IgG2, IgG4, IgA, IgE
- influence plasma vs. memory B cell differentiation
-eosinophil and basophil recriutment
T helper 17 cells
- derived from Th0 by IL-6, TGFB and IL-23
-produce IL-17 and IL-22
-involved in autoimmune diseases (RA, psoriasis and MS) - Anti-fungal
-Increases the production of neutrophils
-Involved in gut inflammation
T regulatory cells (Tregs)
- derived from Th0 by TGFB
- produce IL-10 and TGFB
about 10% of CD4+ T cells
- Natural Tregs
- Induced Tregs
-Regulate T cell activation
-Characterized by CD25+ and Fox P3+
Follicular T cells (Tfh)
derived from Th- by IL-6 and IL-21
-produce IL-21
-Located in germinal centers
-CD4+ and PD-1+
-Activate B cells
- Required for germinal Center B cells to undergo somatic hypermutation
-Important for germinal center B cells differentiation into plasma cells and memory cells
What influences Th cell polarization?
- Type of antigen presentation
- Live vs. dead antigen
-Molecular structure of the antigen
-Route of exposure to antigen
-HLA type of host - determines response of the individual
Th1 stands for
Type 1 immunity
Th2 stands for
Type 2 immunity
Diseases resolving via Type 1 immune response
Tuberculosis
Chlamydia
Leprosy
Intracellular parasites
HIV
Diseases resolving via Type 2 immune responses
Pneumococcal pneumonia
Diphtheria
Meningococcal disease
Helminth (worms)
Diseases caused by Type 1 immune responses
Silicosis
Delayed hypersensitivities
Contact hypersensitivities
Diseases caused by Type 2 immune responses
Allergies
Asthma
Lupus
Activation of CD8+ CTL
Whereas the major function of CD4+ T cell is the production of cytokines, the main function of CTL is cytotoxicity
- aka “Killer T cells” or “T killer cells”, “T cytotoxin cells”
- recognize endogenously produced antigens in association with HLA class I
- Endogenously derived Ag are mostly tumor Ag and Ag from intracellular pathogens (e.g. viruses)
The “kiss of death” or “lethal hit”
- it is unidirectional - only the target cell is killed
- after a brief binding episode, the CTL releases from the target moves on to another target cell
-hours later, the target cells dies
-A single CTL may deliver multiple (>50?) lethal hits before dying
Natural Killer (NK) Cells
- large granular lymphocytes
-come from a common lymphoid stem cell in the bone marrow
-CD56+ and CD16+ but no T cell markers
-no memory- part of the innate response
-Rather than HLA plus antigen peptide, they recognized “a lack of self” through low-level HLA expression
How NK cells recognize foreigness:
-NK possess killer inhibitor receptor (KIRs) that bind HLA class I molecules
- when engaged, killing is inhibited
When HLA class I expression is suppressed in a host cell (e.g. during some virus infections or on some tumors)
KIRs are not sufficiently engaged and killing is allowed
NK cell killing mechanism:
- Similar to CTL with perforins, granzymes, etc.
- can be positively influenced (up-regulated) by IL-2 and IFN-y
- can produce IFN-y
-In addition to tumor killing NK are though to be an important first responder during infections with intracellular pathogens - part of innate defense
Macrophages cytotoxicity
upon activation with IFN-y alone or in combination with other signals, Macrophages have been shown to be cytotoxic
- Two mechanisms are known
Macrophages Cytotoxicity two mechanisms-
TNF-a release and induction of apoptosis
Production of O2 and N2 radicals
Antibody-dependent cell-mediated cytotoxicity (ADCC)
Killer cells (K) for ADCC could be either monocytes, B cells, eosinophils, neutrophils or NK cells
Which molecules are involved in macrophage cytotoxicity?
1. Fc receptors
2. TNFa
3. IgG
4. Oxygen radicals
5. all of the above
- All of the above