This PowerPoint helps students to consider the concept of infinity.
OVERVIEW OF NORMAL IMMUNE SYSTEM
1. PA9.1
DESCRIBE THE PRINCIPLES &
MECHANISMS INVOLVED IN
IMMUNITY
Dr IRA BHARADWAJ
MCI TEACHER ID: PAT 2300569
KUHS FACULTY ID: M21512
2. TEXT BOOK REFRENCES
• ROBBINS BASIC PATHOLOGY
• HARSH MOHAN TEXTBOOK OF PATHOLOGY
• GHAI ESSENTIAL PEDIATRICS
OP GHAI, VINOD K PAUL, ARVIND BAGGA
• TEXTBOOK OF MICROBIOLOGY
DR C P BAVEJA
• OTHER STANDARD REFRENCES
3. SPECIFIC LEARNING OBJECTIVES
• Role of immune system
• Innate immunity
• MPS / RES
• Adaptive immunity: process
• MHC
• Cytokines
• T lymphocytes
• B lymphocytes
• Null cells
• Decline of immunity
• Immunological memory
4. ROLE OF IMMUNE SYSTEM
• PROTECTION OF BODY FROM MICROBES
• PROTECTION OF BODY FROM ABNORMAL SELF CELLS Eg, tumor cells,
cells with intracellular microorganisms
BY
• INNATE IMMUNITY
• ADAPTIVE IMMUNITY
5. INNATE/NATURAL/NATIVE IMMUNITY
INNATE IMMUNITY MEDIATED BY
• EPITHELIUM – which is a physical barrier, and secretes IgA
antibodies,& other anti microbial peptides eg, defensins
(skin), cryptocidins (intestine), histatins (saliva).
• ACUTE INFLAMMATION INVOLVING CELLS like neutrophils,
macrophages [mononuclear phagocytic system], natural
killer cell & CYTOKINES (chemical mediators)
6. MONONUCLEAR PHAGOCYTIC SYSTEM [MPS]
RETICULOENDOTHELIAL SYSTEM [RES]
• Cells of the mononuclear
phagocyte lineage, play a very
important role in immunity
• Many organs contain cells
belonging to MPS as shown in
corresponding diagram
• These cells are derived from
blood monocytes, which are
produced in the bone marrow.
7. ROLE OF INNATE IMMUNITY & ADAPTIVE IMMUNITY
Innate immunity is immediate & via phagocytic cells
Adaptive immunity takes time to develop & is mediated via lymphocytes
8. ADAPTIVE IMMUNITY
PROCESS
Adaptive immunity has to be activated; unlike innate
immunity it is not present spontaneously in the body
Process includes the following :
• Capture & display of antigen [eg,microbial]
• Cell mediated immunity via T lymphocytes
• Cytokine production
• Humoral immunity via B lymphocytes
• Decline of immune response & immunological memory after
the antigen has been neutralized
9.
10. CAPTURE & DISPLAY OF MICROBIAL Ag
Processing of extracellular antigens:
• Extracellular Ags like microorganisms & proteins
[eg bacteria] are captured (taken up) by antigen presenting
cells (APC) eg, DENDRITIC CELLS in the subepithelial tissue
and MACROPHAGES, B LYMPHOCYTES, LANGHERHANS CELLS
at other sites
• This antigen then undergoes intracellular processing, the
end product of this process combines with MHC II molecules
present on APCs
11. CAPTURE & DISPLAY OF MICROBIAL Ag
• APCs also have costimulatory B7 molecules on their cell
surface.
• APCs migrate to lymph nodes
• There the APCs, activate T4 cells by interaction of MHC 2
with T cell receptors (TCR) & B7 with CD28 [present on T L]
Intracellular antigens eg VIRAL Ag & TUMOR Ag
• Intra cellular Ag, combine with MHC I molecules (present on
all nucleated cells ) &
• Activate T8 cells via TCR [T8 cells have receptor for MHC 1]
12. MHC
Major Histocompatibility Complex
• MHC is a genetic “LOCUS” on Chromosome 6p, which codes
for cell surface compatibility i.e., they regulate expression of
cell surface antigen
• Also called HLA (Human Leukocyte Antigens) in humans and
H-2 in mice
• It’s major job is to make sure all self cell antigens are
recognized and “tolerated”, because the general rule of the
immune system is that all UN-recognized cells will NOT be
tolerated
13. MHC MOLECULES
(Gene Products)
MHC 1
• Expressed on all nucleated cells and platelets on the surface
of the cell,
• It is a glycoprotein & antigenic.
• T8 lymphocytes recognize & interact with it to become
activated & cause cytolysis
• They are involved in graft rejection
14. MHC MOLECULES
(Gene Products)
MHC II
• Expressed on all APC’s, i.e., macrophages, dendritic cells & B
lymphocytes on cell surface
• It is a glycoprotein & antigenic
• T4 lymphocytes interact with it and are activated
immunologically
• It is primarily responsible for graft vs host disease
MHC III is related to Complement System Proteins
15. CYTOKINES – chemical messengers
PRODUCED BY
• APC (DC, macrophages ), endothelial cells, lymphocytes,
mast cells & other cells
IN RESPONSE TO
• External stimuli – microbial products, dead cells & other
cytokines
FUNCTIONS
• Innate immunity & inflammation
• Adaptive immunity & Hemopoiesis
16. CYTOKINES – chemical messengers
ACTIONS
• AUTOCRINE, PARACRINE, ENDOCRINE – acting on self, cells in
vicinity, cells at a distance
• PLEOTROPISM, REDUNDANCY – one cytokine has several
functions, one feature eg vasodilatation is controlled by several
cytokines
• EFFECTIVE IN LOW CONCENTRATION, therefore difficult to
measure in clinical labs, tests used only in research labs
• SYNERGY & ANTAGONISM – some cytokines act together, while
other cytokines act against each other
18. CYTOKINES IN ADAPTIVE IMMUNITY
PRODUCED BY ACTIVATED T LYMPHOCYTE
• TH1 cells produce IFN-y
• TH2 cells secrete IL4 , IL-5, IL-13
• TH17 cells produce IL17 & 22 & CHEMOKINES
19. CELL MEDIATED IMMUNITY
T LYMPHOCYTES
• THYMUS DERIVED T L, present in blood, spleen, lymph
nodes, recognize peptides bound to MHC, various subtypes
are -
• T4 ( T HELPER ) ( 60%)
• T8 ( CYTOTOXIC T L ) (40%)
• MUCOSAL T CELLS
• NATURAL KILLER T (NKT) CELLS
• REGULATORY T CELLS
20. T4 (T HELPER) CELLS
• RECOGNIZE PEPTIDES BOUND TO MHC ll (on antigen
presenting cells)
• APC activate naïve T4 cells by binding to TCR & CD28
leading to proliferation & differentiation into various subsets:
TH1,TH2,TH17
These activated subtypes of T4 cells secrete cytokines, which:
• Help B cells in antibody production
• Help macrophages in phagocytosis
• Promote inflammation
21. TH1 subset PRODUCES IFN-y
• TH1 subset is INDUCED by cytokines like, IFN-y [autocrine], IL-12
ACTION
• Activation of macrophages,
• Activates B L to secrete IgG Abs
DEFENCE AGAINST ( NORMAL FUNCTION )
• Intracellular microbes
ROLE IN DISEASE
• Immune mediated chronic inflammatory disease
• Delayed type hypersensitivity reaction [DTH]
22. TH2 subset PRODUCE IL4, IL-5, IL-13
• TH2 subset is INDUCED by IL-4 [autocrine]
ACTIONS
• IL4 – activates BL to secrete IgE Antibodies
• IL-5 - activates eosinophils
• IL-13 -activates mucosal cells to increase mucous secretion,
activates macrophages to secrete GF for tissue repair (fibrosis)
DEFENCE (NORMAL FUNCTION)
• Against helminthic parasites
ROLE IN DISEASE - in allergies [type 1 hypersensitivity reaction]
23. TH17 subset PRODUCES IL17 & 22 &
CHEMOKINES
• TH17 subset is INDUCED by IL-6,1, 23, TGF B
ACTIONS
• Recruit neutrophils & monocytes – promote inflammation
DEFENSE AGAINST ( NORMAL FUNCTION )
• Extracellular bacteria & fungi
ROLE IN DISEASE
• Immune mediated chronic inflammatory disease , often
autoimmune
24. T8 (CYTOTOXIC T L) CELLS
• T8 cells have receptors for MHC l (present on all nucleated
cells, platelets)
• Peptides displayed by MHC l are recognized by T8 L
• Cells bearing MHC l peptides activate T8 L via TCR &
coreceptors
• Activated CTL cause direct killing of infected cells
• Cells expressing ag (peptide) are killed by apoptosis
(granzyme),
• They also secrete cytokines
25. OTHER T CELLS
• MUCOSAL T CELLS – recognize bacterial lipoglycans & act directly
• NK T CELLS - recognize microbial glycolipids & act directly
• REGULATORY T CELLS – suppress immune response
• MEMORY T CELLS – on re-exposure to antigen initiate immediate
specific immune response
28. HUMORAL IMMUNITY
B LYMPHOCYTES
• Derived from bone marrow
• Present in blood, bone marrow, LNs, spleen, tonsils & other
mucosal tissues
• Recognize antigens via B L receptors (IgM/IgD)
• CD 21, receptor for complement also activates B L
• T4 L also activate B L
• Activated B L differentiates to plasma cell, which secretes
antibodies – IgG, IgM, IgA, IgE, IgD
29. ACTIVATION OF B LYMPHOCYTES
occurs by both T cell dependent & independent pathways
T CELL INDEPENDENT
• POLYSACCHRIDE & LIPID Ag + Antigen Receptor on B cells
(IgM/IgD) – ACTIVATE B L- PLASMA CELLS – IgM
• B LYMPHOCYTES ALSO ACT AS APC TO ACTIVATE T CELL
AFTER PROCESSING Ag & COMBINING WITH MHC ll
30. ACTIVATION OF B LYMPHOCYTES
occurs by both T cell dependent & independent pathways
T CELL DEPENDENT
• PROTEIN Ag VIA APCs & T4 - CYTOKINES – BL – PLASMA
CELLS - IgG, IgA, IgE Ab
T LYMPHOCYTE ALSO HELP B LYMPHOCYTES IN
• HEAVY CHAIN CLASS SWITCHING (producing functionally
different Ab [eg IgM to IgG] with same specificity)
• AND STIMULATING PRODUCTION OF ANTIBODIES WITH
HIGH AFFINITY [attraction & binding to antigen]
34. NULL CELLS [non B & T cells active in immunity]
(LARGE GRANULAR LYMPHOCYTES)
THEY ARE FURTHER CATEGORIZED AS :
ANTIBODY DEPENDENT CYTOTOXIC CELL (ADCC)
• Neutralize cells/Ag coated by antibodies
NATURAL KILLER CELL (NKC)*
• Kill tumor cells, virus infected cells & transplanted foreign cells
• Activity is non immune ie, not dependent on MHC or antibody, IL-2 is a growth
factor for these cells
• They act by secreting perforin, which induces apoptosis of cell
LYMPHOKINE ACTIVATED KILLER CELL (LAK)
• Very effective against tumor cells
35. DECLINE OF IMMUNE RESPONSE &
IMMUNOLOGICAL MEMORY
DECLINE OF IMMUNE RESPONSE
After antigen/ microbe is neutralized, activated immune
system returns to normal status by action of suppressor T
cells
IMMUNOLOGICAL MEMORY
Preservation of memory of immune response so next
encounter with antigen directly activates the effector cells
36. DISEASES OF IMMUNE SYSTEM
• IMMUNODEFICIENCY – deficiency, which may be congenital
or acquired
• HYPERSENSTIVITY – inappropriate immune response
• AUTOIMMUNITY- immune reaction against self antigens
• ORGAN TRANSPLANT REJECTION
• AMYLOIDOSIS – deposition of abnormal protein in tissues,
which may be associated with an Immunological cause
