2. Immunology
Study of immune responses to antigen and their
biological, physical and chemical aspects.
◦ Structure & function of immune system
◦ Immunity to disease
◦ Hypersensitivity
◦ Immunization
◦ Transplantation
◦ Tumor immunity
◦ Immunodeficiency
◦ Autoimmunity etc.
3. Immunity -Learning objectives
Function of immune system
Specificity of response
Cell mediated immunity
Antibody mediated immunity
Innate immunity
Adaptive /acquired immunity
Active
Passive
Antigens
Age and immune response
4. Immunity
Micro-organisms are ubiquitous
In spite of constant exposure - long infection-free
periods - is surprising
Infections are exception rather than rule.
Immunity: latin - free of burden.
Development of resistance to a foreign substance
or infectious agent.
Immune: exempted or protected
Immune response: series of defensive actions
5. Categories of Immunity
Innate (natural) immunity
◦ Non specific resistance (immunity) existing in body
prior to exposure to antigens
◦ Include physical, chemical and genetic barriers like
epithelial surfaces, cells, proteins, IFN, lysozyme
complement, inflammation, phagocytosis.
Acquired immunity
◦ Development of specific response to agents like
antigens or infections
◦ improves on repeated exposure
Immunity prevents entry of micro-organisms into
tissues or once entered, eliminates them prior to the
occurrence of disease
6. Innate Immunity
Characteristics
◦Present from birth.
◦Non-specific - acts on many organisms
◦Does not become more efficient on
subsequent exposure to same organisms
◦No memory
◦Acute phase response e.g. C reactive
protein, Mannose binding proteins from
liver
7. Innate Immunity
1. Prevention of entry of organisms
2. Non-specific elimination of micro-organism
3. Activating acquired immunity
Prevention of entry of organisms
Mechanical barriers at body surfaces, skin, mucous
membranes - disruption leads to infection
Antibacterial substances in secretions, lysozyme,
lactoferrin, low pH of stomach and vagina
Prevention of stasis - Peristalsis, Flow of urine,
defecation
Flushing by secretions
Flora, mucociliary blanket, nasal hair
Reflexes of cough, sneezing
9. Innate Immunity
Non-specific elimination of micro-organism
Phagocytosis - ingestion and killing of micro-
organisms by specialized cells (phagocytes) e.g.
◦ polymorphonuclear leukocytes (neutrophils)
◦ mononuclear phagocytes (monocytes,
macrophages), dendritic cells.
Opsonization - the process of coating micro-
organisms with proteins to promote phagocytosis
10. Innate Immunity
Defensins:
◦ Cationic peptide create pores in membranes of
bacterial.
◦ α Defensins in neutrophils in intestines. Also antiviral
◦ β Defensins in respiratory tract
Interferons
◦ Glycoproteins ( cytokines) inhibit growth of viruses by
blocking translation of viral proteins, bacteria, cancer
cells and protozoa. 3 groups
◦ Α Interferons from leukocytes- antiviral
◦ β Interferons from fibroblast- antiviral
◦ γ Interferons from lymphocytes. Mediator of
inflammation
12. Innate Immunity
Inflammation
Opening up of junctions between endothelial cells to
allow plasma proteins to escape
Adhesion of leukocytes to endothelial cells of post-
capillary venule,
followed by emigration of phagocytes into tissues
13.
14.
15. Functions of Innate Immunity
Getting rid of invader
Activation of acquired immunity
Recognize self and non-self proteins.
Pattern-recognition Receptors
Innate arm recognize what is foreign by these
receptors, recognize molecular pattern present on
surface of many microbes that is not present on human
cells – Pathogen Associated Molecular Pattern PAMP
(Carbohydrates, Lipids)
16. Innate Immunity
Pattern Recognition Receptors
Type of receptor activated determine type of acquired
response. 2 types on surface. Toll like receptors and
Mannose binding lectin receptors MBL
Toll Like Receptors TLR: family of 10 receptors on
surface of macrophages, dendritic and mast cells.
Recognize microbial components, activate synthesis of
pro-inflammatory cytokines which initiate immune
response appropriate to type of microbe. E.g. LPS bind
withLPS binding protein transferred to CD14 on
macrophage , stimulates TLR-4 – induce cytokine
production IL1,6,8 and TNF.
Mannose binding lectin MBL: bind to polysaccharide
mannan on bacterial and yeast surface - activate
complement – kill bacteria. MBL also act as opsonin
17. Innate Immunity
Pattern Recognition Receptors
Two types in cytoplasm of human cells.
NOD protein: recognize a part of peptidoglycan in
intracellular bacteria in macrophages,dendritic and
epithelial cells
RIG-1 helicase: recognize nucleic acids of viruses e.g.
orthomyxo, paramyxoviruses
18. Innate Immunity -Acute Phase Proteins
Plasma proteins produced by liver as non specific
response to organisms/antigens. Produced in response
to Pro-inflammatory cytokines IL-1 & IL-6, TNF.
C reactive protein
Mannose binding
lectin MBL
19. Acquired /Adaptive or Specific Immunity
“Specific Immune Response” mounted after exposure to
an agent, improves after repeated exposure.
An immune response must:
Immunological recognition: Recognize a micro-organism as
foreign (non-self) as distinct from self. Diversity
Self/non-self discrimination: The system responds to
micro-organisms but not to its own cells
Immunological specificity: Respond by production of
specific antibodies & specific lymphocytes against specific
antigen. Mediate elimination of micro-organisms
Long term Immunological memory: On subsequent
exposure, the system knows that body has been infected
previously with a particular organism
21. Acquired, Adaptive or Specific Immunity
When occurs in response to microbial infection
The immune system must adapt itself to previously
unseen molecules.
It is activated only after innate arm has interacted
with the microbe
Following recovery from infection, an individual is
protected against that micro-organism. Protection
called acquired “Immunity"
The individual is said to be “Immunized” against that
organism.
22. Acquired, Adaptive or Specific Immunity
Two Components
Cell Mediated Immunity
◦ T Lymphocytes (Helper and Cytotoxic), Antigen
Presenting Cells (APC macrophages, dendritic cells)
Antibody Mediated Immunity
◦ production of antibodies from activated B ceLls-
plasma cells
◦ Neutralize toxins and viruses
◦ Opsonize bacteria (Phagocytosis
23. Acquired, Adaptive Immunity
Active Immunity:
Resistance induced after contact with foreign antigen.
Clinical or subclinical infection, their antigens, live or
killed vaccines or microbial products (toxins, toxoids).
long term resistance, Slow onset
Passive Immunity:
conferred by preformed Antibodies and activated
Lymphocytes
Neutralize toxins. Diptheria, tetanus, rabies, hepatitis
A
Maternal antibodies via placenta (IgG) and milk (IgA).
Short term, prompt availability
24. Innate and Acquired Immunity
Main Features
Humoral Immunity Cell-mediated
immunity
Innate Immunity Complement
Neutrophils
Macrophages
Natural Killer cells,
Dendritic cells
Acquired Immunity B-cells
Plasma cells
Helper T cells
Cytotoxic T cells
Macrophages
Dendritic cells
27. Antigens
Antigen
Molecules which react with antibody
Immunogen
Molecules which induce an immune response
All immunogens are antigens, but all antigens are not
immunogens
Haptens:
small univalent molecules which can react with
specific antibody but not immunogenic. They have to
combine with carrier proteins to be immunogenic.
Able to cross link with antibodies
eg. penicillin, poison ivy.
Haptens can not bind with MHC Class II molecules
but carrier protein can.
28. Antigens
Antigen antibody reaction is highly specific. Lock and
key model
Bind with weak forces such as hydrogen bonds and
vander Waals forces
Affinity (strength of binding) depends upon the fit of
antigen at binding site and ability to form more
bonds. Affinity increases with subsequent exposure.
29. Features of molecule that
determine Immunogenicity
Foreignness: recognized as non self
Molecular size: high molecular weight above 100,000
Chemical Structural complexity: amino acid
homoploymers less antigenic than heteropolymers
Antigenic Determinants (Epitopes): small chemical
groups on antigen molecules which can elicit or react
with the antibody. 5 amino acids or sugars. multivalent
Dosage, Route and Timing of Antigen Administration
30. Effect of age
New born has poor immune response because of:
◦ less effective T cell function
◦ Maternal antibodies decay over 3-6 months
◦ IgA in colostrum.
◦ IgG and IgA begin to be synthesized after birth. Good
response to protein than polysaccharide antigen
◦ More risk of infections
In old age Immunity declines due to:
◦ Reduced IgG response to some antigens
◦ Fewer T cells, Reduced delayed hypersensitivity
◦ More infections. More autoimmune diseases due to
less regulatory T cells- more autoreactive T cells.
