11/26/2014

We already know
Structure & Function of the
Immune System
Lymphocytes
Lymphoid Organs
MHC

Dr Debasis Biswas

Lymphocytes: 20- 40% of WBC populn.

T, B, NK
NK: no surface marker for ag recognition
T, B: Nave Lymphoblasts ..
Effector & Memory
ing Cytoplasm: Nucleus ratio
ing Organellar Complexity (ER; Golgi)

Nave: 6

Lymphoblast: 15

Plasma Cell: 15

B cells

T cells

Maturation: Bursa of Fabricius (birds)

Bone marrow (mammals)
Specific marker for ag recogn: sIg molecule
Soluble ag
Activation.. Blast Transformation & Clonal
Proliferation Effector cells (= Plasma
cells; secrete antibodies) & Memory cells

Maturation: Thymus
Specific marker for ag recogn: T cell receptor
MHC-bound ag on APCs or on virus- infected
cells or cancer cells or grafts
Pan T cell marker: CD3
Helper T cell: CD4; Cytotoxic T cell: CD8
Normally TH: CTL= 2:1

TH cells

CTLs

Activation (MHC Class II)

Blast Transformation &
Clonal Proliferation...
Effector cells
(= Activated Th cells;
secrete cytokines that
activate CTLs, APCs, M,
B cells) &
Memory cells

Activation (MHC Class I)

Blast Transformation &
Clonal Proliferation...
Effector cells
(= Activated CTLs;
eliminate altered self
cells & grafts) &
Memory cells

Effector TH cells

T cells vs B cells
T cells
B cells
T cell Receptor, linked sIg
to CD3
Bind to Sheep RBCs coated
CD2 ag.. Bind to
with Ab & Complement
Sheep RBCs
(CR2 for C3)
Mitogens: PHA, ConA Mitogens: LPS, EB virus
No surface projections Filamentous surface with
microvilli

Cytokine profile
TH2: Supports
TH1: Supports
Inflammation; CMI Humoral immunity

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1ry Lymphoid Organs:

Thymus
Bone Marrow

Lymphoid Organs
Primary Lymphoid Organs Secondary Lymphoid Organs
Maturn. of lymphocytes Interaction of lymphocytes
to achieve ag specificity
with antigen
Thymus (T cells)
Bone Marrow (B cells)

2ry Lymphoid Organs:

Lymph Node
Spleen
MALT
Cutaneous Associated
Lymphoid Tissue

Lymph Nodes
Spleen
Mucosa- Associated
Lymphoid Tissue (MALT)

Thymus

Lymph node
Capsule
Cortex B cells, M, Follicular DCs: 1ry follicle
Ag stimuln
Paracortex T cells, Intdg DCs
2ry follicle with GC
Medulla

Cellular network
to trap antigens
in lymphatic fluid

Cortex: Packed with immature T cells (Thymocytes)

Medulla: Sparsely populated with Thymocytes

Medulla:
Migration of
Plasma cells
from
2ry follicles

Afferent
Lymphatics

Cortex:
2ry follicles with GCs
Cortex:
Migration of B cells &
TH cells to 1ry follicles
Paracortex:
Ag presentn by IDCs

Paracortex
Diffn. into plasma cells
Foci of proliferating B cells

Primary
Lymphoid
Follicles

Germinal
Centers

Spleen

Red Pulp: RBCs; Mes

White Pulp: PALS (T cells)
+ 1ry lymphoid follicles (B cells)
+ Marginal Zone (Lymphocytes + Mes)

Initial activn of B cells

Stimulation of TH cells

Primary
Lymphoid
Follicles

Germinal
Centers

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2ry follicles with GCs

Migration of activated
B & TH cells to 1ry follicles
Marginal Zone:
Ag presentn by IDCs

PALS:
Migration of IDCs
Stimulation of TH cells
Initial activn of B cells

Mucosal Associated Lymphoid

Tissue (MALT)
Mucous memb. of GIT, GUT, Resp. Tract: Major rt.
of ag entry
MALT: Defend these memb surfaces

Splenic
Artery

Tonsils: Lingual; Palatine; Pharyngeal Peyers Patches: Int. submucosa

MALT in Int mucosa

Epithelial layer:
Intra-ep. Lymphocytes (IEL)
mostly T cells
M cells (on inductive site)
Lamina propria:
Loose clusters of B cells,
Plasma Cells, TH cells, M

Submucosa:
Peyers patches with
Lymphoid Follicles

Major Histocompatibility Complex

M cell: Ag entry by endocytosis

Plasma cells: IgA ab

Basolatl pocket: B cells, TH cells, M
Ag delivery to Lymphocytes Activn: B cells in lym. follicles

Structure of MHC molecules

Human: HLA
Chromosome 6

Mouse: H-2
Chromosome 17

Membrane- bound glycoproteins

11/26/2014

Structure of MHC molecules

Class I: 45 kDa chain

+ 12 kDa 2 microglobulin
chain: 1; 2; 3 domains
Between 1 2 domains:
Peptide- binding groove

MHC genes, mRNA transcripts &

protein molecules

Class II: 33 kDa chain

+ 28 kDa chain
chain: 1; 2 domains
chain: 1; 2 domains
Between 1 2 domains:
Peptide- binding groove

Major Histocompatibility Complex

Inheritance of MHC genes

Highly Polymorphic: Many alt. forms of genes (alleles) at each locus
Gene loci lie close together: Low recombination frequency
Genes inherited as 2 sets.. 1 from each parent. Each set: Haplotype
Co-dominant expression: Both parental haplotypes expressed in the
same cells

Class I: All nucleated cells Ag presentn to TC cells

Class II: APCs (DCs, M, B) Ag presentn to TH cells
Class III: Secreted . Assoc. with immune fx & inflammn.

1 in 4 chance siblings have same HLA haplotypes .. Histo-compatible

Recombination within MHC genes

Peptide in the groove

Though infrequent,
Recombination leads to
diversity of alleles
within populations.

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Peptide binding groove

MHC & Disease Susceptibility

Association of some HLA alleles observed with
certain diseases
Quantified as Relative Risk: Frequency of the allele
in the disease populn, compared to general populn

Class I: Groove closed at both ends

Ends of peptide anchored
Peptide: Endogenous; 8- 10 a.a.
Specific a.a. at N & C terminii
Ends fixed with the middle arched
up away from the MHC molecule

Class II: Open ended groove

Peptide: Exogenous;
13- 18 aa;
Binding sites distributed
throughout the groove,
rather than at the ends

Ankylosing Spondylitis... HLA B27 90

Hereditary Hemochromatosis ..A3/ B14 ... 90
Narcolepsy . DR2 130
Insulin Depdt DM DR4/ DR3 .. 20
Goodpastures Syndrome DR2 16

MHC & Disease Susceptibility

Hypothesis:

Specific alleles may account for differences in

the immune responsiveness to particular antigens
arising from variation in the ability to present
processed antigen or the ability of T cells to
recognize presented antigen.

Specific alleles may also encode molecules that

are recognized as receptors by viruses or bacterial
toxins