Sistemul limfatic

Organe si tesuturi limfoide

Cells of the specific immune
system
T cell B cell

Involved with cell mediated

immunity Involved with humoral
Two types: immunity

helper T cells (CD4) Secrete antibodies

cytotoxic T cells (CD8)
Generally eliminate
Generally eliminate extracellular pathogens
intracellular pathogens
Lymphatic System: Overview

Function:

Drain fluid from

around cells
Absorb fat from
intestines
Circulate lymph
Filter lymph
Immunity
ANATOMY OF THE IMMUNE SYSTEM
The immune
system is localized
in several parts of
the body
immune cells
develop in the
primary organs
- bone marrow
and thymus
(yellow)
immune
responses occur
in the
secondary
organs (blue)
The bursa of Fabricius in birds
 Originea celulelor implicate n
rspunsul imun
Celula stem
Hematopoietica Progenitor mieloid
Monocit
GM CSF M CSF

IL1,3,6 G CSF

IL 3
Progenitor
Basofil Macrofag
limfoid IL 5
Celula
dendritica
IL7
B Neutrofil

NK Timus Mastocit

Eosinofil
CD8 CD4
T T

Plasmocit
Lymphocyte Maturation
 ANATOMY OF THE IMMUNE SYSTEM

Bone marrow blood-producing tissue located inside certain

bones (5% BW)
blood stem cells give rise to all of the different types of
blood cells

Thymus glandular organ near the heart where T cells learn

their jobs

Spleen serves as a filter for the blood

removes old and damaged red blood cells
removes infectious agents and uses them to activate cells
called lymphocytes

Lymph nodes small organs that filter out dead cells,

antigens, and other stuff to present to lymphocytes

Lymphatic vessels collect fluid (lymph) that has leaked out

from the blood into the tissues and returns it to circulation
B-CELL DEVELOPMENT
B-CELL DEVELOPMENT
Thymus
A bilobed organ in mediastinum
above the heart
The size of the thymus varies
with age
In infants, it is found in the
inferior neck and extends
into the mediastinum where
it partially overlies the heart
It increases in size and is
most active during childhood
It stops growing during
adolescence and then
gradually atrophies
T-CELL DEVELOPMENT
T-CELL DEVELOPMENT
 Steps in T cell development

Step 1. Positive selection

occurs in the thymic cortex

T cells (CD4+CD8+) that

recognise foreign antigen
presented in the form of
antigen/MHC complexes by
antigen-presenting cells
within the thymus are
allowed to live MHC self-
recognition
molecules

This is called positive

selection
Steps in T cell development
Step 2. Negative selection
occurs in the thymic medulla.

T cells are presented with self

antigen/MHC complexes by
antigen-presenting cells within
the thymus
If T cells bind and recognise
these self antigens they are
destroyed by apoptosis
The immune system destroys T
cells specific for self-antigen

This is called negative

selection
T-CELL DEVELOPMENT

The result is a
T cell
repertoire that
recognises
foreign antigen
and is tolerant
towards self
antigen
Know your Flow!
 Spleen
Largest lymphoid
organ
In upper left
quadrant of
abdomen
Has a hilum and a
capsule
Sinuses contain
blood instead of
lymph

Filters blood
Worn out RBC
Bacteria
Lymphocytes
Monocytes
 Structure of the Spleen
Surrounded by a fibrous
capsule, it has trabeculae that
extend inward and contains
lymphocytes, macrophages,
and huge numbers of
erythrocytes and platelets
Two distinct areas of the
spleen are:
White pulp area
containing mostly
lymphocytes suspended on
reticular fibers and
involved in immune
functions
Red pulp remaining
splenic tissue (MQ)
concerned with disposing
of worn-out RBCs and
bloodborne pathogens
Additional Spleen Functions

Stores breakdown products of RBCs for

later reuse
Spleen macrophages salvage and store
iron for later use by bone marrow
Site of fetal erythrocyte production
(normally ceases after birth)
Stores blood platelets
Lymph

Fluid of the lymphatic system

Similar to blood plasma and interstitial fluid

Lymphatic Vessels

Transport lymph
Lymph is returned to the circulatory system at either the
right or left subclavian veins

Lymph Nodes

500-600, 1-10 mm
Filter lymph, Microorganisms, Cancer cells, Lymphocytes
Monocytes
Lymph Nodes
Lymph is filtered through
lymph nodes
Found in clusters
Vary in size
Principal groupings in deep
thoracic, abdomen and
cervical, axillary, inguinal
regions.
Provide biological filtration
Site of cancer growth and
metastasis
 Lymph Node

Capsule, cortex and medulla:

Cortex contains lymph
nodules
Follicular dendritic cells
Germinal centers B cells
proliferate
Lymphatic vessels enter
node on convex side
Lymph passes through
irregular channels called
sinuses
Leaves node through one
or two efferent vessels at
the hilum or hilus
Flow of lymph
MALT
MALT mucosa-associated
lymphatic tissue is
composed of:
Peyers patches, tonsils,
and the appendix
(digestive tract)
Lymphoid nodules in the
walls of the bronchi
(respiratory tract)
MALT protects the
digestive and respiratory
systems from foreign
matter
Tonsils

Lymphoid tissue of tonsils contains

follicles with germinal centers
Tonsil masses are not fully encapsulated
Epithelial tissue overlying tonsil masses
invaginates, forming blind-ended crypts
Crypts trap and destroy bacteria and
particulate matter
 Tonsils

Simplest lymphoid organs;

form a ring of lymphatic tissue
around the pharynx
Location of the tonsils
Palatine tonsils either
side of the posterior end
of the oral cavity
Lingual tonsils lie at the
base of the tongue
Pharyngeal tonsil
posterior wall of the
nasopharynx
Tubal tonsils surround
the openings of the
auditory tubes into the
pharynx
Aggregates of Lymphoid Follicles

Peyers patches isolated clusters of lymphoid

tissue, similar to tonsils
Found in the wall of the distal portion of the
small intestine
Similar structures are found in the appendix
Peyers patches and the appendix:
Destroy bacteria, preventing them from
breaching the intestinal wall
Generate memory lymphocytes for long-
term immunity
Gut associated lymphoid tissue (GALT) - tonsils,
adenoids, Peyers patches, appendix
Gut associated lymphoid tissue (GALT) - tonsils,
adenoids, Peyers patches, appendix
Lymphatic vessels

Resemble veins (same 3 layers)

Found throughout body except:
Avascular tissues
Central nervous system
Splenic pulp
Bone marrow
Lymphatic vessels join to form
lymphatic trunks

Lymphatic trunks
join to form :
Thoracic duct
(3/4 of body)
Right lymphatic
duct (drains right
arm, and right side
of head, neck and
upper torso)
These empty into
subclavian veins at
junction with
internal jugular
vein.
 Fluid Movement

Formation of lymph:

Fluid leaves capillaries by

diffusion and filtration
Escaped proteins

If lymph flow blocked =

tissue swelling or edema

Specialized lymphatic
capillaries in vili of small
intestine transport lipids -
they are called lacteals, and
the fluid is called chyle.
Edema
Accumulation of
interstitial fluid
Causes of Edema
Blockage of lymphatic
system
Increased pressure in
veins
Lack of albumin
Decreases fluid
returning to blood
capillaries by osmosis
Inflammation
 Overview of the immune response:

Antibody
mediated
Cell (humoral)
mediated
(CMI)

(Fig. 22.6, p. 762, Madigan et al.)

Antigen Recognition

Provides the key for the immune system

to recognize the presence of
intracellular microorganisms
MHC proteins are ignored by T cells if
they are complexed with self protein
fragments
Antigen Recognition

If MHC proteins are complexed with

endogenous or exogenous antigenic
peptides, they:
Indicate the presence of intracellular
infectious microorganisms
Act as antigen holders
Form the self part of the self-antiself
complexes recognized by T cells
T Cell Activation: Step One
Antigen Binding

TC cells are activated by antigen fragments

complexed with class I MHC proteins
APCs produce co-stimulatory molecules that are
required for TC activation
TCR that acts to recognize the self-antiself
complex is linked to multiple intracellular signaling
pathways
Other T cell surface proteins are involved in
antigen binding (e.g., CD4 and CD8 help maintain
coupling during antigen recognition)
T Cell Activation: Step One
Antigen Binding

Figure 21.16
T Cell Activation: Step Two
Co-stimulation
Before a T cell can undergo
clonal expansion, it must
recognize one or more co-
stimulatory signals
This recognition may require
binding to other surface
receptors on an APC
Macrophages produce
surface B7 proteins
when nonspecific
defenses are mobilized
B7 binding with the CD28
receptor on the surface
of T cells is a crucial co-
stimulatory signal
Other co-stimulatory signals
include cytokines and
interleukin 1 and 2
T Cell Activation: Step Two
Co-stimulation

Depending on receptor type, co-stimulators can

cause T cells to complete their activation or
abort activation
Without co-stimulation, T cells:
Become tolerant to that antigen
Are unable to divide
Do not secrete cytokines
T cells that are activated:
Enlarge, proliferate, and form clones
Differentiate and perform functions
according to their T cell class
 Cytokines

Mediators involved in cellular immunity, including

hormonelike glycoproteins released by activated T
cells and macrophages
Some are co-stimulators of T cells and T cell
proliferation
Interleukin 1 (IL-1) released by macrophages co-
stimulates bound T cells to:
Release interleukin 2 (IL-2)
Synthesize more IL-2 receptors
Cytokines

IL-2 is a key growth factor, which sets up

a positive feedback cycle that encourages
activated T cells to divide
It is used therapeutically to enhance the
bodys defenses against cancer
Other cytokines amplify and regulate
immune and nonspecific responses
Helper T Cells (TH)
Helper T Cell
TH cells interact directly
with B cells that have
antigen fragments on
their surfaces bound to
MHC II receptors
TH cells stimulate B cells
to divide more rapidly and
begin antibody formation
B cells may be activated
without TH cells by
binding to T cell
independent antigens
Most antigens, however,
require TH co-stimulation
to activate B cells
Cytokines released by TH
amplify nonspecific
defenses
 Cytotoxic T Cell (Tc)
TC cells, or killer T cells, are the only T cells
that can directly attack and kill other cells
They circulate throughout the body in search
of body cells that display the antigen to which
they have been sensitized
Their targets include:
Virus-infected cells
Cells with intracellular bacteria or parasites
Cancer cells
Foreign cells from blood transfusions or
transplants
T-CELL FUNCTIONS
T-CELL FUNCTIONS
Mechanisms of Tc Action

Figure 21.18a, b
A Cytotoxic T Cell Attacking and Killing a Virus-
Infected Target Cell

CELLS alive!

Here, the smaller cytotoxic T cell or Tc (arrow) is attacking and killing a

much larger virus-infected cell. The T cell will survive while the infected
cell is destroyed.
Other T Cells

Suppressor T cells (TS) regulatory

cells that release cytokines, which
suppress the activity of both T cells
and B cells
Gamma delta T cells (Tgd) 5 10% of
all T cells found in the intestines that
are triggered by binding to MICA
receptors
 Selection of B cells by antigen (clonal selection)

Different types of B cells have

different receptor molecules.

When a pathogen (germ) locks
on to a receptor, that type of B
cell is selected.

The selected B cell divides
rapidly to make lots of copies
of itself. The copies make lots
of antibodies against the
pathogen.
Plasma cells secrete antibody at a high rate but can no longer respond to
antigen or helper T cells.
 Clonal Selection Theory (continued)

Some of the cells

become plasma
cells that secrete
primary response.
Others become
memory cells that
secrete
antibodies during
the secondary
response.
Antigens select
lymphocytes that
are already able
to make
antibodies.
Memory & specificity key features
of the adaptive immunity
Cinetica rspunsului imun la o infecie
viral tipic