!!

Lymphoid Organs
Primary lymphoid organs:

- Bone marrow
- Thymus
the cells of the immune system
originate in and mature here

Secondary lymphoid organs:

- Spleen
- Lymphatic vessels
- Lymph nodes
- Adenoids and tonsils
- MALT (Mucosal Associated Lymphoid Tissue)
GALT (Gut Associated Lymphoid Tissue)
BALT (Bronchus Associated Lymphoid Tissue)
SALT (Skin Associated Lymphoid Tissue)
NALT (Nasal Associated Lymphoid Tissue)
not for cell development. (final differentiation, activation may be
performed) The cells of the adaptive immune system recognize
here the pathogens
 THE TWO ARMS OF THE IMMUNE
SYSTEM
!!
Monocytes, Macrophages, Dendritic
Monocytes, Macrophages, Dendritic
cells, Granulocytes, NK cells and B and T cells
cells, Granulocytes, NK cells and
Complement components
Complement components

MEMORY
 Professional phagocytic cells
macrophages !!
neutrophyl granulocytes
dendrtitic cells

Professional antigen presenting cells

macrophages
B lymphocytes !!
dendrtitic cells

they express MHCII molecules

the protein degradation products (peptides) can be presented

to T lymphocytes by MHC molecules
Cells of innate immune system:

Macrophages:
 Macrophages are constitutively present in tissues and recognize microbes that enter these
!!
tissues and respond rapidly to these microbes. Initiate the immune response
• These cells are phagocytes (eliminate the pathogens)
• Activate the innate immune response (by secreted proteins, called cytokines)
• Activate the adaptive immune system. Macrophages serve as APCs that display antigens to
and activate T lymphocytes

• Dendritic cells
are constitutively present in tissues and recognize rapidly microbes that enter these tissues.
Initiate the immune response.
• They have phagocytic capabilities
migrate to lymph nodes, and display microbial antigens to T lymphocytes,professional antigen
presentimg cells (APC)

Neutrophil granulocytes
are phagocytes, the main function to eliminate the pathogens
Appear only in the circulation under normal condition
Main actors In inflammatory processes
 Innate immunity as a first line of defence
!!

Innate immune cells recognize frequently found structures of

pathogens by PRRs ,
these are not found in human cells!
PRRs (pattern recognition receptors) are responsible for recognize conserved
structures of the microbes

Examples of recognited structures:

duple strain RNA
bacterial cell wall components
bacterial flagellin….

Recognition is inevitable
 Danger signal!
The innate immune system also recognizes molecules that are released from damaged or
!!
necrotic cells. Such molecules are called damage-associated molecular patterns (DAMPs).
 OPSONIZATION
!!
Opsonization facilitate and accelerate the recognition of the pathogen by phaogocytes,
opsonins form a bridge between pathogen and a phagocyte connecting them.

Main opsonins:
antibodies
Complement fragments
Acute-phase proteins
 Specificity of innate immunity

direct connetion
between innate cells
and pathogen
( )

Few receptors (20-30) are responsible for the recognition of all the pathogens
 T cell receptor (TCR)
!! The TCR, which recognizes peptide antigens displayed by MHC molecules

BCR

V
sH
s s
s
s s
s
VL s
C
s H1
s s
s
s s
s
CLs s
s
s
s

ss
ss
CH2ss ss

CH3ss s
s

:
• membrane-bound heterodimer composed of an α chain and a β chain, each chain
containing one variable (V) region and one constant (C) region Both the α chain
and the β chain of the TCR participate in specific recognition of MHC molecules
and bound peptides
TCRs only function as membrane receptors
!!

B cell Plasma cell

TCR

T cell
 ANTIGEN RECOGNITION BY T-CELLS REQUIRES
PEPTIDE ANTIGENS AND ANTIGEN PRESENTING CELLS
THAT EXPRESS MHC MOLECULES

II T
!!
Cell surface MHC-
peptide complex
soluble Ag Peptide
antigen
Native Cell surface
membrane Ag peptides APC
APC
APC

No T-cell response T-cell response

 MHCI
! !
Expressed by all nucleated cells

STRUCTURE OF CLASS I MHC MOLECULES

PEPTIDE

2 1

2m
3
 MHCII
! !
Expressed by professional antigen presenting cells
Macrophage, dendritic cell, B cell

STRUCTURE OF CLASS II MHC MOLECULES

PEPTIDE

1 1

2 2
 ANTIGEN RECOGNITION BY T-CELLS REQUIRES
PEPTIDE ANTIGENS AND ANTIGEN PRESENTING CELLS
THAT EXPRESS MHC MOLECULES

II T
!!
Cell surface MHC-
peptide complex
soluble Ag Peptide
antigen
Native Cell surface
membrane Ag peptides APC
APC
APC

No T-cell response T-cell response

 !!
MHCI

Displays intracellular antigens

to cytotoxic T cells
 !!
MHCII

Displays extracellular antigens

to helper T cells
 RECOGNITION OF EXOGENOUS AND ENDOGENOUS ANTIGENES
BY T-LYMPHOCYTES
! !
Tc Th

TCR TCR

Peptide Peptide

MHCI MHCII
Exogenous Ag
Endogenous Ag
APC

Peptides of endogenous proteins Peptides of exogenous proteins (toxin,

(virus, tumor) bind to class I MHC bacteria, allergen) bind to class II MHC
molecules presented to cytotoxic T molecules presented to helper T cells
cells
 !!
T cell receptor (TCR) recognizes peptide antigen and
simultaneously
also recognizes the MHC molecule that is displaying that peptide
 Specificity of innate immunity

Specificity of T cells

Tc Tc
Distinct T cell receptors peptid

Peptides derived MHC

from different microbes

APC APC
 Specificity of innate immunity

direct connetion
between innate cells
and pathogen
( )

Specificity of T cells

T T
Distinct T cell receptors peptid No direct
connetion
Peptides derived
MHC
between T cell
from different microbes and pathogen
APC APC
APC-T cell connection
 Immunoglobulin STRUCTURE !!
• 2x identical Heavy chain (light blue)

• 2x identical light chain (dark blue)

• Variable regions  antigen binding

disulfide bond
• Constant regions carbohydrate

CL
VL
CH2 CH3
CH1

hinge region
VH
ANTIBODY DOMAINS AND THEIR FUNCTIONS

Antigen recognition
!!
antigénkötés sVH
s s
s
s
VL s

s
s
CH1
Variable domain
variábilisdomének s
s

s
s

s
s
CL

s
s s

s
s

s
ss
ss
Constant domain
konstansdomének CH2ss s
s

effektorfunkciók CH3ss s
s

Effector functions
 BCR (B cell receptor) Antibody
!!

Transmembrane
Associated chains domain
for signaling

Cytoplasmic
domain SOLUBLE (freely circulating)
MEMBRANE BOUND! Antigen recognition and effector
Antigen recognition and B cell functions.
activation Produced by plasma cells
 ! !
B cell epitop T cell epitop

B cells recognize: T cells recognize:

proteins peptides (8-23 amino acid)

polysaccharides
lipids only when these peptides are
DNS presented by MHC molecules on
steroids APC cells
drugs, etc

Tissue or soluble antigens

 Receptors responsible for the recogniton of pathogens in the immune system

Caracteristics of innate PRR Pattern recognition Danger signal and

immune system, receptors Pathogen recognition
macrophage, dendritic cells mainly in the innate immun
system
B cells BCR (B cell receptor) Antigen recognition of B
cell
T cells TCR (T cell receptor) Antigen recognition of T
cell
All nucleated cells in MHC (MHCI) Major Do not recognise
human Histocompatibility pathogens, but present
Complex intracellular peptides
required for T cell receptor

professional antigen MHCII Do not recognise

presenting cells: pathogens, but present
macrophages, DC, B cells extracellular peptides
required for T cell receptor
 THE TWO ARMS OF THE IMMUNE
SYSTEM
!!
Monocytes, Macrophages, Dendritic
Monocytes, Macrophages, Dendritic
cells, Granulocytes, NK cells and B and T cells
cells, Granulocytes, NK cells and
Complement components
Complement components

MEMORY
 BCR (B cell receptor) Antibody
!!

Transmembrane
Associated chains domain
for signaling

Cytoplasmic
domain SOLUBLE (freely circulating)
MEMBRANE BOUND! Antigen recognition and effector
Antigen recognition and B cell functions.
activation Produced by plasma cells
 !
Several antibodies are expressed on B cells, (arround 100.000) but all of them with the
same specificity
!
 !!
Antigen recognition by specific BCR induces clonal expansion and
differentiation of the sepcific B cells.

Plasma cells,
antibody
Antigen
production
2.Differen
Activation of
tiation
specific B cells
1. Clonal
expansion

Antigen

MEMORY B CELLS
Antigen Antigen
Antigen
Effector funtions

Innate
Adative
B cells
T cells

Extracellular
Intracellular pathogens
 INNATE IMMUNITY II
!!

Effector functions, elimination of pathogens

1. Phagocytosis
2. Killing with soluble mediators
3. Complement system
4. NK cell activation
 !!
EFFECTOR FUNCTIONS OF ANTIBODIES

Antibody-mediated immune responses

• NEUTRALIZATION
• OPSONIZATION
• COMPLEMENT FIXATION
• ADCC
• MAST CELL DEGRANULATION
 ! !
T helper cells (TH cells) assist other white blood cells in
immunologic processes

Cytotoxic T cells (TC cells, or CTLs) destroy virally

infected cells and tumor cells
 !!
Activation of helper T cells results in cytokine
production
 THE MOST IMPORTANT FEATURES OF CYTOKINES
 Cytokines are the most important mediators of indirect cell communication in the
immune system („hormones” of the immune system).
!!
 !!
MHCI is present in all the nucleated cells
Intracellular pathogens can be presented on all the cells
Any cell is infected, can be killed by cytotoxic T cells

MHCII present extracellular antigens to helper T cells. Helper T

cells direct the immun eresponse by the pruduced cytokines.
 THE TWO ARMS OF THE IMMUNE
SYSTEM
!!
Monocytes, Macrophages, Dendritic
Monocytes, Macrophages, Dendritic
cells, Granulocytes, NK cells and B and T cells
cells, Granulocytes, NK cells and
Complement components
Complement components

MEMORY
 !
B cell memory:
!
Quicker response
Increase in the number of specific B cells
The amounts of antibody are biger
Higher affinity antibodies (‘more specific’)
Isotype switch

In case of T dependent B cell activation

 !
!

T cell memory:

Quicker response
Increase in the number of responding cells
!
!
 Active and passive immunization
!!
active passive

protection slow immediate

(2 weeks)
Time-span long short
(years)
protection

passive
active

injection time