Day 21 - 13/10/14 Flashcards
What are Alpha-Beta T Cells called before they recognise their SPECIFIC foreign antigen?
Naive
What is the percentage of T-Lymphocytes and alpha-beta-T-Lymphocytes respectively?
70% of lymphocytes are T-Lymphocytes
95% of T-Lymphocytes are Alpa-Beta Lymphocytes
What happens when T cells recognise their specific foreign antigen on APCs?
1) T Cells undergo cell division called CLONAL EXPANSION
2) Then they DIFFERENTIATE in to EFFECTOR CELLS
What can you say about TCR and BINDING?
TCR cannot bind on its own
CO-STIMULATORY molecules
- allow TCR to bind to APC
- initiate important signalling
What structure forms at the point of contact between APC and TCR?
IMMUNE SYNAPSE
What is the structure of IMMUNE SYNAPSE?
1) ADHESION MOLECULES such as LFA-1 , ICAM-1
form a TIGHT RING on the T CELL and APC membranes
2)The TCR and the COSTIMULATORY molecules are held in place at the centre
What can you say about COSTIMULATORY MOLECULES in context of their presence in cells?
They are INVARIENT
-do not differ on different cells and are NOT specific
Name major and additional COSTIMULATORY Molecules.
CD3
CD4
CD8
CD28
CD80
CD86
Additional
CD40
OX40
ICOS
What does CD3 do?
CD3 has long CYTOPLASMIC TAILS which bind and activate TYROSINE KINASES.
This initiates INTRACELLULAR SIGNALLING after specific antigen detection.
What does CD4 do?
CD4 binds to CLASS 2 MHC to make the TCR to PEPTIDE-MHC binding better.
CD4 also drags the enzyme: Ick
to CD3.
CD3 can then begins to RECRUIT SIGNALLING ENZYMES
inside the T CELL.
What does CD8 do?
Same as CD4, but binds to
CLASS 1 MHC and Ick
What does CD28 do?
Binds to CD80 and CD86 on the APC.
This LIGATION triggers signalling which is essential to TRANSCRIBE and make INTERLEUKIN 2 (IL2)
What does IL2 do?
IL2 and IL2 RECEPTOR is made by CD4+ cells.
AUTOCRINE interaction between these two result in
CLONAL EXPANSION
What happens if you don’t have COSTIMULATORY MOLECULES?
T-Cells become TOLERANT of antigens and is unable to respond to them in the future.
What do CD40ligand, OX40 and ICOS do?
After CLONAL EXPANSION, differentiation of the TCELL occurs.
What APC presents antigens in a way that PRIMES NAIVE CD4+ T Cells?
Dendritic Cells
Dendritic Cells are SENTINELS.
What does this entail?
Sample the environment by
- Endocytosis
- Pinocytosis
- phagocytosis
What happens when Dendritic Cells find antigens?
Dendritic Cells leave the tissue via AFFERENT LYMPHATICS and then enter the T-Cell area of the LYMPH NODES.
There they activate the corresponding CD4+ NAIVE T CELLS
How is the Dendritic Cells activated?
Dendritic Cell is ACTIVATED by DANGER SIGNALS such as picking up components of Bacteria/Viruses with the TOLL LIKE RECEPTORS (TLR)
What do the DANGER SIGNALS do?
Increase ANTIGEN PROCESSING
and CCR7 CHEMOKINE RECEPTOR needed to drive Dendritic Cells to the LYMPH NODES
Increase expression COMPLIMENTARY MOLECULES
CD40
CD80
CD86
Define Immunological Tolerance
A state of antigen specific unresponsiveness to an antigen which
Under other circumstances can stimulate an active immune response.
What happens if Tolerance doesn’t work?
AUTOIMMUNITY
What does Tolerance usually happen to?
Food Proteins
Commensal Microbes
Foetus
Give examples of Tolerance diseases
Coeliac disease - allergic for wheat protein
Crohn’s disease - allergic to commensals
What are the two types of tolerance?
- Central
- Peripheral
(tolerance)
What is CENTRAL tolerance?
Tolerance against SELF ANTIGENS
Affected Cells- T&B lymphocytes
Affected Organs- THYMUS & BONE MARROW
What is PERIPHERAL tolerance?
Tolerance against
- HARMLESS FOREIGN ANTIGENS
- SPECIFIC SELF ANTIGENS (e.g. During lactation milk/Sex hormones)
Affected Cells - MATURE LYMPHOCYTES
Affected Organs - Secondary Lymphatic organs
What are the 4 cellular mechanisms of Tolerance?
Ignorance
Clonal Deletion
Clonal Anergy
Active Regulation
When does IGNORANCE occur?
Lymphocytes which aren’t usually exposed to tissue antigens and so cannot make an immune response.
(Such as lens of the eye/testis)
When does CLONAL DELETION occur?
When MATURING lymphocytes encounter SELF ANTIGENS in the THYMUS/BONE MARROW.
Self-Reactive T-Cells die.
When does CLONAL ANERGY occur?
Occurs when MATURE T LYMPHOCYTES
encounter SELF/FOREIGN ANTIGENS
presented by APC
in the ABSENCE of COSTIMULATORY molecules
Can happen in BONE MARROW or
PERIPHERAL IMMUNE SYSTEM
When does ACTIVE REGULATION occur?
REGULATORY T CELLS
against SELF ANTIGENS in THYMUS
or FOREIGN ANTIGENS in PERIPHERAL NERVOUS SYSTEMS
