1) The document discusses the lymphatic and immune systems, including lymphoid organs, lymphocytes, antigen presentation, and the major histocompatibility complex. 2) It describes T lymphocyte development and function, including the roles of CD4+ and CD8+ T cells. 3) The roles of B lymphocytes and antibody production are summarized.

1. DR. SHILPA SONI
MGMCH, JAIPUR

2. LympRetic
syst
Lymphoid
sys
Lymphoid
cells
Lymphd
organs
Retic sys
Phagocytic
cells

3. • Thymus
• BM
Central(1*)lympd
organs
(precursor Lmpc
proliferates,dev
& mature)
• LN,spleen
• Mucosa associated
lympd tissue
Peripheral (2*)
lympd organs

5. Lymphocytes- T- lymph
B- “
Null cells/large granular lymphocytes
-ADCC-antibody dependent cell mediated cytotoxic lymp.
-NK cells
Reticular sys cells-Phagocytic cells- macrophages & microphages
Macrophg -monocytes(in Bd) largest of lymp cells.
-Histiocytes(in tissues)-microglia in CNS
-Kupffer cells in
liver
-alveolar macrophages
in lungs
-osteoclasts in bone
-sinushistiocytes in spleen. LN
Microphg -polymorphnuc cells of Bd- N,E & B.
Dendritic cells-dentritic, langerhans, follicular dendritic cells

6. Located at short arm of Chr-6, codes for
histocompatibility (transplantation )Ag.
Binds peptide fragments of foreign Pr. for
presentation to appr. Ag specific T cell.
Classified as-
Class-I
• Gps,on all nuc.
Cells & plt
• Presn Ag to CD
8
• Graft rejectn &
cytolysis
Class-II
• Gps, on APCs-
macrophg,Dcs,B
cells
• Ag to CD 4
• Graft vs host
rxn & mixed
leukocyte rxn
Class-III
• Soluble prt of
complement sys
• Heat shock prt
• TNF α
• TNF β

8. Human body contains
10¹² lymphocytes out
of which 10^9 are
renewed daily.
Mature B & T cells
before encountering
Ag are K/A Naïve
cells.
Types- T lymphocytes
- B “

9. NormalPercentage Lymphocytes: 15-40%
of White Blood Cells
Total Lymphocytes: 800-2600/mm³
Total T Lymphocytes: 800-2200/mm³
T helper Cells: >400/mm³
T suppressor Cells: 250-750/mm³
Helper Cell to Suppressor Cell ratio: >0.9
CD2 Percentage of Lymphocytes: 65-85%
CD4 Percentage of Lymphocytes: 45-75%

11. Thymus derived lympc- 60-70% of periph lymphoc.
Found in- paracortical areas of LN.
- periarteriolar sheeths of spleen.
Ag + TCR -> signal 1
All T cells contain CD 3 molecule->signal 1
Surface mol or receptors of T cells-
CD 2
CD 4 – 60% of T cells
CD 8 – 30% of T cells (cytotoxic)
CD 11a
CD 28 – binds to B 7-1(CD 80) & 7-2(CD 86) of APCs ->
signal 2
CD 40

12. CD8/CTL
CD4/TH cells
1) TH1 - inflammatory response
2) TH2 - anti-inflammatory, B cell response
3) Treg - inhibit immune responses

16. T cells:
Development in thymus
Migration out of thymus into blood
(Naïve T cells)
Priming phase: Antigen-dependent
differentiation in lymphoid tissues
(to become memory and effector T cells)
Effector phase: Migration to sites of
infection and effector function
Human:
Fetal development
Birth
School
Job

17. Immunology’s Secret”
1) Early experiments demonstrated that antigen-derived
(i.e. TCR-mediated) signals alone are insufficient to
initiate an immune response
2) A second substance - an “adjuvant” - is required to
prevent the induction of tolerance
3) In vitro, triggering the TCR alone also leads to a
tolerant state (known as “anergy”)
4) “Two-Signal Hypothesis”: Activation of a naïve T cell
requires signals from both the TCR (antigen-specific)
and a second, co-stimulatory receptor (antigen-
independent)
5) Adjuvants work in part by inducing antigen presenting
cells to express ligands for co-stimulatory receptors

21. Green: MHC class II
Red: Lysosomal protein

23. Polarization of T Cells Part I: The Cytoskeleton
1) T cell responses are directed at the
APC/target cell, not in all directions
2) This requires reorganization of the cell to have
a “front” (toward the APC) and a “back” -
induced by signals from the TCR and
costimulatory molecules
3) Result: Reorganization of the cytoskeleton
causes reorientation of cytosolic organelles
toward APC - Golgi, secretory vessicles, and
microtubule organizing center (MTOC). The
MTOC connects actin cytoskeletal changes
with the tubulin cytoskeleton

24. Fig. 8.29 The polarization of T cells during specific antigen recognition

25. Polarization of T Cells Part II: Lipid Rafts
1) Lipid rafts - also called GEMs (glycolipid enriched
microdomains) and DIGs (detergent-insoluble glycolipid-
rich domains) - are plasma membrane microdomains
2) Enriched in cholesterol, glycolipids, and sphingolipids
(i.e. lipids that are not glycerol-based), making them
more rigid than the surrounding membrane
3) Some membrane proteins are segregated - selectively
enriched or depleted in rafts. Many key signaling
molecules (esp. src-family kinases) are constitutively
localized to lipid rafts.
4) Dynamic structures - small rafts can condense to form
larger rafts
5) During T cell activation, TCR, CD28, and many adhesion
molecules are recruited into lipid rafts, where they can
interact with signaling molecules

28. The T cell antigen receptor
Va Vb
Ca Cb
Carbohydrates
Hinge
Transmembrane regionCytoplasmic tail
++
+
Antigen
combining site

29. The Immunologic Synapse - Putting it Together
1) The combination of cytoskeletal rearrangement and lipid raft
redistribution leads to the formation of a Supramolecular Activation
Complex (SMAC) - a highly ordered arrangement of receptors, adhesion
molecules, and signaling molecules

30. Th2
Additional Figures

31. T cells
CD 4 (60%)
also k/a Th/inducers/TH 0 cells.binds MHC II
TH1
Secretes IL-2,IFN-γ
Facilitates delayed
hypersens,macroph.
Activatn,synth of IgG2 Abs
TH2
Secretes IL4,IL5
Facilitates synth of all Abs
except IgG2
CD8(30%)
cytotoxic T cells
Or suppressor cells
Binds to MHC I
Secretes IL2, INFγ
Facilitates type 2
hypersensitivity.

33. The disorder is
mediated largely by
CLA(cutaneous
lymphocyte
associated antigen)-
positive, CD8+ T cells
with type 1 cytokines
(interferon-g,
interleukin-2, and
lymphotoxin); these
cells may be
activated by an
autoantigen in skin

34. It is mediated by
CLA-positive,
CD8+ effector T
cells that recognize
contact-sensitizing
antigens.
The activated T
cells have a variable
cytokine profile
(e.g., both type 1
and type 2
cytokines).

35. initiated by CLA-positive,
CD4+ T cells with type 2
cytokines (interleukin-4, 5,
10, and 13). T cells that
produce type 1 cytokines may
be involved in persistent
lesions

36. The transformed T
cells are found
throughout the
dermis and in the
epidermis. Many
reactive
(nontransformed)
CLA-positive T cells
are also present in
lesions.

37. CLA-positive T cells producing
type 1 cytokines (in acute
disease) or type 2 cytokines
(in chronic disease)
are present in lesions.

38. Other T cell- skin disorders
-LP
-Eczemas
-Pneumocystis jiroveci pneumonia
and cryptosporidiosis.

39. T-cell defects
-Wiskott–Aldrich syndrome (WASP gene
mutations)
-Ataxia telangiectasia (ATM mutations)
-Chronic mucocutaneous candidiasis (AIRE,
FoxP3 deficiency)
-X-linked hyper-IgM (CD40 ligand deficiency);
autosomal hyper-IgM syndrome
(multiple defects)
-Cartilage–hair hypoplasia
-Idiopathic CD4+ T-cell lymphopenia

40. 10%- 20% Of periph lymphoc
Humoral immunity
Presents in BM, peripheral
lymphoid tissues-superficial
cortex of LN, white pulp of
Spleen, tonsils & extra
Lymphatic organs e.g GIT
Responds to free Ag
Acts as APC
Ag binding compon-IgM

41. Other molecules are complement receptor,
Fc receptors, CD 21 – recept for EBV, CD 40-
essential for intraction of T & B cell -> B cell
maturation (mutation in CD 40 ligand cause
immunodeficiency called X-linked hyper IgM
syndrome.

42. B cell development in the bone marrow
B Regulates construction of an antigen receptor
Bone Marrow provides a
MATURATION & DIFFERENTIATION MICROENVIRONMENT
for B cell development
Ensures each cell has only one specificityB
Checks and disposes of self-reactive B cellsB
Exports useful cells to the peripheryB
Provides a site for antibody productionB

43. in bone marrow
* The lymphoid stem cells differentiate into B cells
* B-cells precursors mature, differentiate into
immunocomptent B-cells with a single antigen specificity
* Immature B-cells that express high affinity receptors for self
antigens, die or fail to mature
i.e negative selection or clonal deletion
* This process induces central self tolerance and reduces
autoimmune diseases

44. B
B
Stromal cell

45. Bone marrow stromal cell
Maturing B cells

46. Stages of differentiation in the bone marrow are
defined by Ig gene rearrangement
B CELL STAGE
IgH GENE
CONFIGURATION
Stem cell Early pro-B Late pro-B Large pre-B
Germline DH to JH VH to DHJH VHDHJH
Pre-B cell
receptor
expressed
Ig light chain gene has not yet rearranged

47. * Immature B cells - IgM receptors on the surface
* Mature B cells - IgM, IgD molecules on surfaces
IgM and IgD molecules serve as receptors for antigens
* Memory B-cells - IgG or IgA or IgE on the surface
* B-cells bear receptors for Fc portion of IgG and a receptor for C3
component of the complement
* They express an array of molecules on their surfaces that are
important in B-cells interactions with other cells such as MHC II,
B7 and CD40

51. Structure & functions
Definition: Glycoprotein molecules that are produced by
plasma cells in response to an immunogen and which
function as antibodies.
* Produced by:
B-lymphocytes in response to exposure to antigen
* React specifically with antigen
* Five classes of Antibodies:
IgG
IgM
IgA
IgD
IgE

52. Immunoglobulins are glycoproteins made up of
- Four polypeptide chains (IgG):
a- Two light (L) polypeptide chains
b- Two heavy (H) polypeptide chains
- The four chains are linked by disulfide bonds
- Terminal portion of L-chain contains part of antigen binding site
- H-chains are distinct for each of the five immunoglobulins
- Terminal portion of H-chain participate in antigen binding site
- The other (Carboxyl) terminal portion forms Fc fragment

53. - Each H-chain and each L-chain has V-region and C-region
- V-region lies in terminal portion of molecule
- V-region shows wide variation in amino a. sequences
- Hypervariable region form region complementary to Ag
determinant
- It is responsible for antigen binding
- C-region lies in carboxyl or terminal portion of molecule
- C-region shows an unvarying amino acid sequence
- It is responsible for biologic functions

55. Fab fragment: antigen binding site
Fc (crystallizable fragment):
a- Complement fixation (IgM and IgG)
b- Opsonization (IgG)
C- Placental attachment (IgG)
d- Mucosal attachment (IgA)
e- Binding to mast cells (IgE)

57. roperty
IgG IgA IgM IgE IgD
Heavy chain
symbol
γ α µ ε δ
Molecular
weight
150
KDa
170-400
KDa
900
KDa
190
KDa
180
KDa
Percentage
in serum
75 % 15 % 10 % 0.004 % % 0.2
Complement
fixation
Yes No Yes No No
ansplacental
passage
Yes No No No No
Opsonization Yes No No No No

58. Primary antibody respone Secondary antibody response
* first exposure to antigen * Subsequent exposure
* lag period: days or weeks * Lag period: hours
* Small amount immunogl. * large amount immunogl.
* in Weeks then decline * Persist for long periods
* Antibody is IgM * Antibody is IgG

59. -X-linked agammaglobulinaemia
-μ-chain deficiency; surrogate light-chain
deficiency
-SWAP-70 deficiency
-Hyper-IgE syndrome (includes secondary
neutrophil disorder)
-CD79a (Igα chain) deficiency
-BLNK deficiency
-ICOS deficiency
-TACI deficiency

61. T cells B cells
•Ab binding site Ag rec (TCR with
CD3)
Surface Ig
•Fc receptor — +
•Complement
receptor
- +
•EAC rosette-
C 3, CR 2, EBV rec
- +
•E/SRBC rosette-
Cd 2, measles rec
+ -
•Microvilli on surface - +
•Thymus specific Ag + -
•Blast transformation Occurs by anti CD 3,
phytohemagglutinin,
concanavalin
Occurs by anti Ig
endotoxin, staph
aureus, EBV

62. -Severe combined immunodeficiency (RAG-1/RAG-
2 mutations, common γ-chain deficiency; CD3ε
deficiency)
-Adenosine deaminase deficiency
-Purine nucleoside phosphorylase deficiency
DNA repair defects (DNA ligase IV); Bloom’s
syndrome; xeroderma pigmentosum
-Canale–Smith syndrome (autoimmune
lymphoproliferative syndromes; fas, fas-ligand,
caspase deficiencies)
-X-linked lymphoproliferative syndrome (SAP
deficiency; includes NK disorder)

64. Increased (Lymphocytosis)Increased
Absolute Lymphocyte Count (>4500/mm3)
Non-activated Lymphocytes
 Influenza
 Pertussis
 Tuberculosis
 Mumps
 Varicella
 Herpes Simplex Virus
 Rubeola
 Brucellosis
 Chronic Lymphocytic Leukemia
 Acute Lymphoblastic Leukemia

65. Activated Lymphocytes (Atypical
lymphocytes)
Cytomegalovirus Infection
Infectious Mononucleosis
Infectious Hepatitis
Toxoplasmosis
Post-transfusion
Medication
 Mephenytoin
 Dilantin
 Para-aminosalicylic acid

66. Increased Relative Lymphocyte Count
Normal finding in children under age 2 years
Acute stage of viral infection
Connective tissue disease
Hyperthyroidism
Addison's Disease
Splenomegaly

67. Decreased
AIDS
Bone Marrow suppression
Aplastic Anemia
Neoplasms
Steroids
Adrenocortical hyperfunction
Neurologic Disorders
 Multiple Sclerosis
 Myasthenia Gravis
 Gullain Barre Syndrom