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Introduction to the immune system

Kusworini Handono
Faculty of Medicine, Brawijaya University
Malang
What is the immune system?
The body’s defense against disease causing organisms,
malfunctioning cells, and foreign particles
Physiologic function of the immune system

• Defence against infectious microbes and tumor


• The defence is mediated through early reactions of
innate immunity and the latter responses of adaptive
immunity
• There two types of adaptive immune responses, called
humoral immunity and cell mediated immunity, that are
mediated by different component of the immune system
and function to eliminate different types of microbe
The most important physiologic function of the
immune system is to prevent or eradicate infections
Defense Mechanisms of The Human Host

• Innate Mechanisms (Innate immunity)


– First line of defense
– Non-specific

• Adaptive Mechanisms (Adaptive immunity)


– Second line of defense
– Highly specific with memory

• Cooperation between mechanisms


Immune System
Microbe
Innate immunity Adaptive immunity
B lymphocytes Antibodies
Epithelial
barriers

T lymphocytes
Effector T cells
Phagocytes

Complement NK cells

Hours Days
0 6 12 1 3 5
Time after infection
Innate Immunity
• Consist of cellular and biochemical defense mechanisme
that are in placed to response rapidly to infection
• Provides the early lines of defense against microbes
• The principal component :
1. physical and chemical barrier : epithelial surfaces and
antimicrobial substances produced at epithelial
surfaces.
2. phagocytic cells (neutrophils, macrophages, NK cells),
3. blood protein (complement system and other
mediator of inflammation)
4. proteins (cytokines).
Adaptive Immunity
• Immune responses that are stimulated by exposure to
infectious agents and increase in magnitude and
defensive capabilities with each succesive exposure to a
particular microbe
• Are exquisite specificity for disticnt molecules and an
ability to remember and respon more vigorously to
repeated exposures to the same microbe
• Is able to recognize and react to a large number of
microbial and non microbial subtances
• Component : lymphocytes and their product (antibodies)
Tissues of the immune system
Anatomy and functions of lymphoid tissues

• Generative ( primary ) lymphoid organs :


- bone marrow, where all the circulating blood cells
(including lymphocytes) arises and the site of B cells
maturation
- thymus, where T cells mature and reach a state of
functional competence

• Peripheral ( secondary ) lymphoid organs, where


lymphocyte responses to foreign antigens are initiated
and develop : lymph nodes, the spleen, the mucosal
and cutaneous immune systems
Bone Marrow : Hematopoiesis
Bone Marrow and Thymus : Maturation of lymphocyte
Lymphnodes, spleen and the lymphatic system

• Lymph nodes are the organs in which adaptive immune


responses to lymph-borne antigens are initiated
• Different classes of lymphocytes are sequstered to
distinct regions of lymph nodes
• Antigens are transported to lymph nodes mainly in
lymphatic vessels
• The spleen is the major site of immune responses to
blood-borne antigens
Morphology of a lymph node
Segregation of B cells and T cells in lymph node
Spleen
The lymphatic system
Cells of the Immune System
20
Macrophages
• Macrophages are white blood cells that engulf and destroy
foreign (non-self) antigenic molecules, viruses or microbes
and then display small fragments of the antigen on the outer
surface of their plasma membrane
• Macrophages are related to dendritic cells
Maturation of mononuclear phagocytes
Phagocytosis
Phagocytosis
Neutrophiles
NETOSIS :
activation neutrophile cell death

Neutophile
Extracellular Traps
NETs : Neutrophile
Extracellular Traps

The function of NETs is to


trap and to kill
extracellular microbes
Natural Killer cells

Mechanisms in Rheumatology ©2001


Function of Natural Killer cells
Antigen Presenting Cell / APC

• APCs are cells specialized to capture microbial and other


antigens, display them to lymphocytes, and provide signals
that stimulate the proliferation and differentiation of the
lymphocytes.
• The type mayor of APC : DC (initiating T cell responses),
Monocyte/macrophage (present Ag to T cell during CMI), B
cell (for Th cell during humoral IR) , FDC (few cells in the
lymph node, spleen and mucosal lymphoid tissue) a
Dendritic Cells
Antigen presentation and recognition
Lymphocytes

• The only cells capable of specifically recognizing and


distinguishing different antigenic determinants and are
therefore responsible for the two characteristics of
adaptive immune response : specificity and memory
• Lymphocytes consist of distinct subsets that are different
in their functions and protein products but are
morphologically indistuinghable
Lymphocytes classes % total lymphocytes
Classes Functions Markers blood Lymph Spleen
node

T helper Stimuli for B cell growth CD3+,CD4+ , 50-60 50-60 50-60


(Th1, and differentiation CD8-
Th2, (humoral immunity)
Th17) MØ activation by secreted
cytokines (CMI)
T Killing of virus infected CD3+,CD4-, 20-25 15-20 10-15
cytolytic cells,tumor cells;rejection CD8+
of allograft ( CMI)
B cells Antibody production Fc rec, MHC-II , 10-15 20-25 40-45
( humoral immunity) CD19 ; CD21

T reg Supression T cell and B CD3+, CD4+ ? ? ?


cells activation CD25+, FoxP3
NK cells Killing of virus infected Fc rec for IgG -10 Rare -10
cells,tumor cells; ADCC
T helper lymphocytes subset
The function of T lymphocytes
Role of B lymphocytes

• B cells act as antigen


presenting cells (APCs),
presenting antigen
to T cells
• B cells secrete antibodies
(immunoglobulins)
T helper 17

 Subset of Th cells producing IL-17, IL-22


 Cytokines contribute in their formation : TGF-β, IL-6, IL-
21 and IL-22
 Protein involve in their differentiation : STAT3, RORα,
RORϒ
 Natural function of these cells are recruitment, migration
and activation of neutrophyles in anti-microbial
immunity at epithellial and mucosal barrier
 Play a key role in autoimmune disease specifically
inducing inflammation and tissue injury
Surface markers of Th17
Regulatory T lymphocytes / Treg

 Subset of T cells that activelly supress variety physiological


and pathological immune responses
 The function : maintenance of immunological self tolerance
and immune homeostasis
 10 % of total CD4 T cells, express CD4+, CD25+ and Foxp3
 There are 2 source of Treg : nTreg (tTreg) and iTreg (pTreg)
 nTreg : expression of the transcription factor forkhead
boxp3 (Foxp3) occur in thymus
 iTreg : expression of Foxp3 induced in pherypheral
The Humoral Immune Response

Mechanisms in Rheumatology ©2001


Effector Mechanisms of Immune
Response : Cellular Immunity
The Cells Mediated Immune Response

Click here to run the animation

Mechanisms in Rheumatology ©2001


Maturation of T cells in the thymus