T Cells, HIV Flashcards
Ratio of T cell in lymphocyte population
Two-third of circulating lymphocytes
Origin and Maturation of T cells
Origin: Bone marrow
Maturation: Thymus gland
Origin and maturation:
T cells VS B cells
B cells are manufactured and matured in bone marrow
T cells are manufactured in bone marrow BUT maturation takes place in thymus gland
Process of maturation of T cells
- Auto-reactive cells are removed
- Then they develop into either T helper cells OR cytotoxic T cells
Which class of HLA is recognised by helper T cell and cytotoxic T cell?
- Cytotoxic T cell recognises class-I HLA
- T-helper cell recognises class-II HLA
Which clusters of surface antigen (= CD: Clusters of Differentiation) are expressed by T cells?
All T cells express CD3
- CD4 is conserved among helper-T cells (CD4+ helper-T cells)
- CD8 is conserved smong cytotoxic T cells (CD8+ cytotoxic T cells)
Can we distinguish T cells under light microscopy?
NO
All T cells look much the same under light microscopy
Investigation to distinguish T cells
Flow cytometry
How do we distinguish T cells by flow cytometry?
We identify clusters of surface antigen ( = Clusters of differentiation = CD)
All T cells express CD3
Only T helper cells express CD4
Only cytotoxic T cells express CD8
Which CD (Clusters of differentiation) is “Common” to be expressed by CD4+ helper-T cells and CD8+ cytotoxic T cells?
CD3
T-helper cells: Common subtypes
- Th1
- Th2
- Th17
The most aggressive phenotype of T-helper cell
Th-1
The most tolerant phenotype of T-helper cell
Th-2
Which type of T helper cell has a prominent inflammatory response?
Th-1
What can trigger type-1 T-helper cells (Th-1)?
Cytokines (such as IFN: Interferon)
>>> resulting in a hostile environment for pathogens
What can trigger type-2 T-helper cells (Th-2)?
Cytokines, such as: Interleukin-10 (IL-10)
Th-2: Functions
- Associated with “humoral response”
- Drives antibody class switching
Give an example when Th-2 predominates
Pregnancy
Predominant subtype of T-helper cells in Pregnancy
Th-2
Recent sub-type of T-helper cell
Th-17 (T-helper cell type 17)
What does activate Th-17?
IL-17
Which type of T cells are current subject of pharmaceutical trials across a borad range of diseases?
Th-17 (along with its activator IL-17)
Cell that provides immune system a “window” into other cells
T lymphocytes
Cell that is especially imporant defence against intracellular pathogen
T cells
Association of T cells with autoimmunity
Normal function of T cell is essential to prevent autoimmunity
What is genetic predictor of autoimmune disease & example?
Genetic predictor is the genetic code for HLA on chromosome 6
Example:
- HLA-DR4 >>> Rheumatoid Arthritis
- HLA-Cw6 >>> Psoriasis
Name a T-cell deficiency disease
HIV AIDS
Main effect of HIV on T cells
HIV causes progressive depletion of CD4 T-helper cell population
Which type of T cell is affected/depleted by HIV?
CD4 T cells
How does HIV deplete CD4 T cells?
- IL-2 (a cytokine) is central to T cell proliferation
- HIV supresses IL-2 >>> induced T-cell deficiency state
Which type of cytokine is supressed by HIV?
IL-2 (interleukin-2)
Similarity of “mechanism” between “HIV infection” and “Ciclosporin or Tacrolimus drugs”
Both inhibit IL-2
Similarity of “side-effects” between “HIV infection” and “Ciclosporin or Tacrolimus drugs”
Both cause same pattern of opportunistic infection (as both inhibit IL-2)
- TB (Tuberculosis)
- Pneumocystis Jerovecii
- Disseminated viral disease
“Opportunistic infections” that are common between “HIV infection” and “Ciclosporin or Tacrolimus drugs therapy”
- TB (Tuberculosis)
- Pneumocystis Jerovecii
- Disseminated viral disease
Number of ‘specific’ receptor on lymphocytes (B cell or T cells)
Each individual lymphocyte expresses a “single type of receptor” with “unique specificity” (except dual specificity T cells)
Type of receptor on B cell and T cell
- B cell receptor >> memrane bound immunoglobulin (IgM monomer or IgD isotype) >> recognises particular Ag
- T cell receptor >> TCR (T cell receptor) complex: a heterodimer >> recognises peptide fragments (presented by MHC molecules)
Where is the ‘antigen specificity’ of B cell and T cell generated?
- For B cells >> bone marrow
- For T cells >> Thymus
When is the ‘antigen specificity’ of B cell and T cell generated?
During development (at maturation phase)
How is the ‘antigen specificity’ of B cell and T cell generated?
By recombination of gene segments encoding the variable domains (antigen recognition domains) of immune receptors
- These gene recombinations are random
- Maturing lymphocytes that express autoreactive receptors >>> then deleted or rendered anergic
Are all autoreactive lymphocytes deleted duting development?
NO
Not all autoreactive lymphocytes are deleted during development.
In the case of T lymphocytes,
- NOT all proteins are expressed in the thymus
AND the proteins that are present only in the periphery OR at certain stages of development >>> will encounter mature T cells that can respond to them.
>>> Thus, autoreactive T cells exist in the periphery (and other mechanisms are responsible for the protection of the body against autoimmunity)
