Immunology

Dr. Kanwal Hassan Cheema

Assistant Professor
Microbiology
Learning objectives

• Definitions
• Cells involved in the immune response
• Types of immunity
• Innate
• Acquired
1. Humoral
2. Cell mediated
An overview

Immunity: protection against infectious and non-

infectious foreign invaders

Immune system: collections of cells and molecules that

defend against microbes
Importance in Health & Disease

Essential for survival

Immunodeficiency Syndromes
Innate
Acquired
Important role in pathogenicity of:
 Autoimmunity
 Hypersensitivity
Transplant rejection
Organs and tissues involved in immunity

1. Primary lymphoid organs:

 Bone marrow
 Thymus

2. Secondary lymphoid organs:

 Lymph nodes
 Spleen
 Mucosal-associated lymphoid tissue(MALT)
Major Components of the immune system

Lymphocytes ( B cells and T cells)

 Phagocytic cells

 Complement
Types of Immunity

I. Innate (Natural) immunity/ AKA Non-specific Immunity:

 First and second line of defense
 Intrinsically present
 Immediately available
 Non- specific
 No immunologic memory
 Limited diversity
Types of immunity

II. Adaptive (acquired) immunity/Specific Immunity:

Third line of defense
 Activated on antigen exposure
Available days after antigen exposure
More effective
 More specific
More diverse
Has immunologic memory
Types of Immunity (Active Vs Passive)

I. Active Immunity:
Resistance induced after contact with foreign antigen
a. Naturally Acquired Active Immunity
b. Artificially Acquired Active Immunity

II. Passive Immunity:

Resistance by giving preformed antibodies
a. Natural passive immunity
b. Artificial passive immunity
ANTIGENS?

• Substances capable of inducing a specific immune response.

• Foreign macromolecules or cells induce an immune response leading
to :

 Production of proteins called antibodies (by B cells)

 Production of specifically reactive lymphocytes (T cells)

EPITOPES?

 Antigenic determinants
Determinant groups.
• Sites either on or within the antigen with which antibodies react.
Physical properties: small e.g. 4 or 5 amino acids or monosaccharide
residues

 determine specificity
 Antibodies are specific for epitopes
 First line of Defense
Acts as a mechanical
Intact skin barrier

Lysozyme in tears Degrades peptidoglycan

Respiratory cilia Traps organisms; prevent
Entry

Low pH in stomach and Retards microbial growth

vagina; fatty acids in skin

Defensins (cationic peptides) Creates pores in bacterial cell membrane

Normal flora of throat, Occupy receptors; prevent
colon and vagina colonization by pathogens
 Second Line of Defense

 Phagocytic cells

 Natural killer cells

 Complement system

Interferons
Natural Killer cells

5-10% of peripheral lymphocytes

 AKA large granular lymphocyte
 An important role in innate immunity
 Do not require thymus for development
Do not possess specialized cell surface receptors like T or B cells
Specialize in killing virus-infected cells and tumour cells
Activity not enhanced by prior antigen exposure
Do not have memory
Mechanism of killing

 Perforins
Granzymes
Fas-Fas ligand mediated cell death
 ADCC ( antibody dependent cellular cytotoxicity)
What is phagocytosis?

 Literally means “ eating up”

It is a process of engulfment of microbes by
phagocytic cells eventually resulting in killing of these
microbes
Steps involved in Phagocytosis

1. Attachment
2. Extension of pseudopodia to engulf the attached
material
3. Formation of a phagosome
4. Fusion of the phagosome with a lysosome to form a
phagolysosome
5. Intracellular killing
6. Release of digested contents
 Neutrophils

 Most abundant white blood cell (40-75%)

First cell to arrive at the site of infection or
inflammation
 Multi-lobed nucleus
Cytoplasmic granules which stain pink
These granules are lysosomes which contain various
degradative enzymes responsible for bacterial killing
Anti bactericidal action

1. OXYGEN-DEPENDENT MECHANISMS:
a. NADPH oxidase enzyme
b. Myeloperoxidase enzyme
2. OXYGEN-INDEPENDENT MECHANISMS:
a. Lysozyme
b. Defensins
c. Lactoferrin
d. Hydrolytic enzymes
 Macrophage

• Circulating in blood: monocytes

• Fixed in tissues: macrophages
• Various names according to anatomical location:
1. Kupffer cells: Liver
2. Microglial cells: brain
3. Histiocytes : connective tissue
4. Langerhans cells: skin and mucosa
5. Alveolar macrophages: lung alveoli
Functions

1. PHAGOCYTOSIS:
Engulfment and subsequent killing of microbes
2. ANTIGEN PRESENTATION:
Present antigen to T cells and activate them and help in the
adaptive arm of immunity
3. CYTOKINE PRODUCTION:
Produce several cytokines like interleukin-1, and TNF and IL-8
4. TISSUE HEALING AND REPAIR:
Secrete EGF, TGF-alpha, PDGF and FGF that help in wound healing
and tissue repair
Interferons

Glycoprotein in nature
Usually produced in response to viral infection
Species specific
Not virus specific
Three types
1. Alpha
2. Beta
3. Gamma
Interferons

1. Interferon-alpha:
• Source: Leukocytes
• Function: inhibit viral replication by inhibiting viral mRNA translation

2. Interferon-beta:
• Source: Fibroblasts
• Function: same as INF-alpha
Interferons

3. Interferon-gamma:
• Source: lymphocytes
• Function:
• Increase phagocytic activity of macrophages
• Anti-tumor activity
• Enhancement of cell-mediated immunity
Therapeutic uses of Interferons

• Used in the treatment of hepatitis B and hepatitis C

• Certain cancers like leukemia and melanoma
• Multiple sclerosis
Complement system

 Consists of 20 proteins present in serum

 Synthesized in liver
 Participates in innate as well as acquired arms of the
immune system
 Proenzymes enzymatically cleaved in a cascade to form
active enzymes
Complement is activated by three pathways:
1. Classical
2. Alternate pathway
3. Lectin pathway
• Complement activation results in the formation of a
MEMBRANE ATTACK COMPLEX ( MAC) and other proteins
that play an important role in innate immunity
Biologic effects of activated complement
products
1. Opsonization: C3b
2. Chemotaxis : C5a
3. Anaphylatoxins : C3a, C4a and C5a
4. Cell lysis: MAC
5. Enhancement of antibody production: C3b