lecture slides on introduction to immunology by Dr. Naeem (RMC)

1. Introduction to
Immunology

2. MICROBES IN
ENVIRONMENT
AirWater Soil
HUMAN
Attack
Naeem
Microorganisms are found everywhere in the
environment human encounter is inevitable
Among thousands of microbial species
probably 300-400 cause diseases in humans

3. Immunology
• Is the study of our protection from foreign macromolecules or
invading organisms including viruses, bacteria, protozoa or
parasites and our responses to them
• The host response consists of:
o Non-specific or innate immunity.
o Specific or adaptive immunity.
In addition, we develop immune responses against
 our own proteins (and other molecules) as in
autoimmunity
 against our own aberrant cells as in tumor immunity
 exaggerated immune response to foreign molecules as in
hypersensitivity

4. NON-SPECIFIC IMMUNITY
• Resistance that exists prior to the
exposure to the antigen
ELEMENTS
• Anatomical barriers: Skin & MM
• Secretary molecules
• Cellular components
• Involves processes like phagocytosis and
inflammation

5. Protective Characteristics of the Skin
Outer (dermal) layers
• Keratin layer: physical barrier to microbial penetration
• Sloughing of outer layers removes attached bacteria
• Dry & acidic conditions limit bacterial growth
Hair follicles, sweat & sebaceous glands
• Production of acids, toxic lipids & salts
that limit bacterial growth
• Skin-associated lymphoid tissue
Naeem

7. Secretary Molecules
• Skin
o Organic acids, toxic lipids & salts in secretions
• GIT
o Thiocyanate & lysozymes in saliva: degrade
peptidoglycan in bacterial cell wall
o Low pH in stomach: bactericidal
o Fatty acids & bile acids in the lower GI tract

8. Defenses after invasion by
microbes
Non-specific Defences
Phagocytes : ingest & destroy bacteria.
Inflammation : if microbes survive
encounter with phagocytes:
Natural Killer Cells
Interferon
Specific Defenses
Antibody-mediated immunity
Cell-mediated immunity
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9. Secretary Molecules
• In serum
o Transferrin & lactoferrin: sequester iron required for
bacterial growth
o Interferons: Inhibit viral replication
o Complement: Cause bacterial killing
o Acute phase proteins: ‘CRP’ bind to bacteria and activate
complement
o Defensins: create pores in bacterial cell
o Primarily located in GIT (α-defensin) & LRT (β-defensin)
o Lysozymes in tears & secretions: bactericidal

10. Cellular Components
Phagocytic cells
Neutrophils (polymorphonuclear: PMN)
o Are the most important cellular components in bacterial
destruction
o Are relatively large and most abundant WBCs with lobed
nucleus and cytoplasmic granules (lysosomes) containing
degradative enzymes

11. •Mononuclear Phagocytes: Include
o Monocytes in circulation
o Histiocytes in tissues
o Microglilal cells in the brain
o Kupffer cells in the liver
o Macrophages in serous cavities and lymphoid organs
o Participate in both innate (bacterial killing) & acquired immune
responses (APC)
Cellular Components
Phagocytic cells

12. Monocyte Neutrophils
Monocyte with ingested
malarial parasite
Macrophages
attacking E. coli

13. • All phagocytic cells have receptors for a variety of
molecules like:
o IgG Fc
o Complement
o Interferon
o TNF
o Certain bacterial components
• Receptor interactions with these ligands promote
phagocytosis and activation for efficient killing of
pathogens
Cellular Components
Phagocytic cells

14. Non-specific Killer Cells
NK and LAK cells
ADCC (K) cell
Activated
macrophages
They all kill foreign
and altered self
targets

15. Natural Killer (NK) cells
• Named NK cells because:
 they are active without prior exposure to the virus
 are not enhanced by exposure and
 are not specific for any virus
• Are large granular lymphocytes (LGL)
• Up to 15% of blood lymphocytes
• Do not need thymus for development
• Lack T-cell receptor
• Lack T CD3 proteins and surface IgM & IgD

16. Natural Killer (NK) cells
• Kill virus-infected cells
 Killing is non-specific and is not dependent on foreign antigen
presentation by of class I or II MHC and
 kill by secreting perforins and granzymes
• Kill malignant cells by recognizing a protein MICA on many
cancer cells which is not found on normal cells
• Interaction of MICA with receptor on NK cells triggers
secretion of cytotoxins and death of tumour cell

17. Natural Killer (NK) cells
Can kill without antibodies but IgG
enhances their activity, a process
called Antibody-Dependent Cellular
Cytotoxicity (ADCC)
Activated by IL2 and IFN-γ to become
LAK cells

18. NK Cells Activation

19. • Three groups based on cells of origin
 Alpha INF by leucocytes
 Beta INF by fibroblasts
 Gamma INF by lymphocytes
• Alpha & Beta INFs are induced by viruses
• Gamma INF is induced by antigens and is one of the effectors of cell
mediated immunity
INTERFERONS

20. Alpha & Beta Interferons
• Are group of proteins produced by human cells
primarily after viral infection
• DNA & RNA viruses are competent inducers
• dsRNA are better inducers: dsRNA poly (rI-rC) is one
of the strongest inducers and was under
consideration as antiviral agent but toxic effects
prevented its clinical use.
Other Inducers
• Intracellular bacteria and protozoa
• Bacterial endotoxins

21. Alpha & Beta Interferons
• Are non-specific for any particular virus
• Inhibit intracellular viral replication without effect
on normal cells : selective toxicity
 Is due to presence of dsRNA in virus infected cells and
not in uninfected cells
• Have no effect on extracellular virus particles
• Are typically host specific : other animals can not
be used as source of INFs for human therapy

22. Alpha & Beta Interferons
• INF binds to cell surface receptor and induce the cell to
produce three proteins : are activated by dsRNA in virus-
infected cells
 Oligo A synthetase activates RNAse
 RNAse that degrades viral & cellular mRNA
 Protein kinase that inhibit protein synthesis
• Inhibit viral & cellular protein synthesis and leads to death
of infected cell and no viral replication and no spread
• Are produced within a few hours of viral replication and act
in early phase of viral infection

23. • Alpha INF: Chronic active hepatitis due to HBV & HCV
and condyloma acuminatum
• Beta INF : Multiple sclerosis
• Gamma INF : Chronic granulomatous diseases
• Anti-cancer uses: Kaposi’s sarcoma and hairy cell
leukoplakis which are due to oncogenic viruses
Alpha & Beta Interferons
Clinical Uses

24. Differences between the two types of immunity
Specific ImmunityNon-specific Immunity
Highly specificNon-specific
Response is antigen dependentResponse is antigen-independent
There is a lag time between exposure and
maximal response (in days)
There is immediate maximal response
(within minutes)
Antigen-specificNot antigen-specific
Exposure results in immunologic memory
Exposure results in no immunologic
memory

25. Physico-chemical barriers to infections
Effector MechanismActive componentSystem/Organ
Desquamation; flushing, organic
acids
Squamous cells; SweatSkin
Peristalsis, low pH, bile acid,
flushing, thiocyanate
Columnar cellsGI tract
Mucocialiary elevator, surfactantTracheal ciliaLung
Flushing, lysozymeMucus, saliva, tearsNasopharynx and eye
Phagocytosis and intracellular
killing
Direct & antibody dependent
cytolysis,
IL-2 activated cytolysis
Phagocytic cells
NK-cells, K cells &
LAK
Circulation and lymphoid organs
Iron bindingLactoferrin and TransferrinSerum
Antiviral proteinsInterferons
antiviral, phagocyte activationTNF-alpha
Peptidoglycan hydrolysisLysozyme
Opsonization and phagocytosisFibronectin
Opsonization, enhanced
phagocytosis, inflammation
Complement