T-cell & B cell receptors – role in immune response & Major Histocompatibility Complex...

T-cell & B cell receptors – role in immune response

&

Major Histocompatibility Complex (MHC)

Lecture 64/10/2015

Effective Immune Response Requirementsالفعالة المناعية االستجابة متطلبات

I. Lymphocytes

II. Antigen presenting cells (APC)

Lymphocytes display receptors

لألرتباط مستقبالت تحملالغريبة باالنتيجينات

• Specificity• diversity• Memory• Self- Non- Self Recognition

B-Lymphocytesالعظام نخاع في وتنضج تنشأ

Naive B cell + Antigen(Ag) divide and replicate (proliferate)

(BCR)الذاكرة Memory B cell خاليا

الفعالة Effector B cell الخاليا

Plasma cell (antibody secreting cell)

B cell receptor (BCR) = surface antibodies

Plasma cells short livedMemory B cells long lived

B-Lymphocytes activation

الغدة في وتنضج العظام نخاع في تنشأالسعترية

Thymus gland T cell receptor = TCR

TCR Ag molecules on MHC

Ag presentation تقديماالنتجين

MHC-I MHC-II

recognize

T-Lymphocytes

الذاكرة خالياMemory T cell

الفعالة الخاليا Effector T cell

Divide and replicate (proliferate)Naïve T cell + Ag

T-Lymphocytes activation

Structure of T cell and B cell receptors

T cell and B cell receptors

T cell subset & functions

CD8+ T cells (cytotoxic T cell = Tc)

• Cytotoxicity

• Bind antigen associated with MHC- I

CD4+ T cells

• Bind antigen associated with MHC- II

1- T- helper cell (TH2) ….. Helper cells for B cells

2- T- helper cell (TH1)

• Helper cells for cytotoxic T cells.

• Helper cells for macrophage activation

3- Regulatory T cell (Treg cell) …..Regulation & suppression

Antigen Presenting cell (APC)

• Ability to ingest, process and present antigen

• Express MHC class II, co-stimulatory molecules

For example:

1. Langerhans cells 2. Macrophages (MФ)3. Dendritic cells (DC)

4. B cells

Antigen recognition by T cells (1)

• Only recognise cell-bound antigen

• Recognise antigen in association with HLA

CD4+ T cells - Recognise foreign antigenic peptide in

context of self MHC class II (Fig. b)

CD8+ T cells - Recognise foreign antigenic peptide in

context of self MHC class I (Fig. a)

Antigen recognition by T cells (2)

T cells & B cells – differ their methods of antigen recognition

B cells/antibodies can recognise whole native proteins

T cells do not require native protein – recognition of denatured protein is possible

Regulatory T cell (Treg cell)

• Recently described CD4+ CD25+ population

• Depletion results in autoimmune disease

• Suppress both CD4+ and CD8+ T cells

• Regulate T cell responses

• May explain T cell ‘suppression’

Lymphocyte subsets

Activate B cellsand macrophagesT HELPER CELLS

Th

Kill virus-infected cells

CYTOTOXIC TLYMPHOCYTES

CTL

Produce antibodiesPLASMA CELLS

PC

T B

T CELLS B CELLS

CLP

Commonlymphoidprecursor

Major Histocompatibility Complex = MHC

HLA = Human Leucocyte Antigen = Human MHC

MHC structure

MHC peptide binding groove

MHC Class II molecule

• Expressed by ‘professional’ APCs:

MФ, DCs, B cells

• Bind peptides from exogenous antigens

• Peptides are 12-20 amino acids in length

• Restriction element for CD4+ T cells

MHC class I molecule

• Expressed by most nucleated cells

• Bind peptides from endogenously synthesised antigens

• Peptides are 8-11 amino acids in length

• Restriction element for CD8+ T cells

Interaction between T cells and MHC-peptide complex