Innate Immunity

Dr. Nadisha Badanasinghe

Senior Lecturer
 Objectives
• What is innate immunity?
• Components of innate immune response
• Differences b/w innate and acquired
responses
• Recognition, Activation and Elimination by the
innate immune response
 What is immunity?

Defenses to avoid infection, disease or other

unwanted biological invasion

What is immune response?

Response to harmful agents

What mediates it?

By the immune system
 What is immune system?
• The immune system is a network of
– cells (neutrophils, macrophages, lymphocytes)
– tissues /organs (bone marrow, thymus, lymph nodes, spleen)
– molecules (cytokines, complements)
that work together to defend the body against attacks by “foreign”
invaders.

• It is the immune system’s job to keep them out or, failing that,
to seek out and destroy them.

• It can recognize and remember millions of different enemies,

and it can produce secretions and cells to match up with and
wipe out nearly all of them
 How does the immune system work against
pathogens?

• The immune system must be able to differentiate between

material that is a normal component of the body (“self”) and
material that is not native to the body (“nonself”)

• A highly specialized receptors present for discriminating

between ”self” and “nonself” body components
What are the types of immune responses?
• Mainly two types

1) The innate (natural or nonspecific) immune response

- Born with it

2) The adaptive (acquired or specific) immune response

- stimulated by microbes
1. humoral - by antibodies secreted by B cells
2. cell mediated – by T cells

These two systems perform many of their functions by cooperative interactions

 Defenses

1) Innate immunity (Natural or Non specific)

2) Acquired immunity (Adaptive or Specific)

Cell-mediated immunity Humoral immunity

 Innate Immunity
• Born with it
• Natural/ native
• First line of defense
• Non specific
• No immunologic memory
• Non adaptive
 Innate Vs. Adaptive
• Born with it • Stimulated by m.o
• 1st line- acts immediately • 2nd line- takes time
• Less specific • Specific
• No memory • Memory
• Only acts on foreign substances • Can act on self tissues
• Recognize broad molecules on
pathogens • Recognize specific
molecules (Antigens)
 What are the components of immune
system?
Innate immunity Adaptive immunity

Humoral Cell-mediated

Components Components
Macrophages antigen presenting cells
Granulocytes T-cells
Natural killer cells B-cells
Complement Antibodies
Other chemicals: HCL, lysozyme Complement

Characteristics
* Action is immediate
* Response is non-specific
* Response is not enhanced on
repeated exposure to pathogen
( no memory)
Characteristics
* Action is delayed
* Response is specific
* Response is enhanced on
repeated exposure to pathogen
( has memory)
 Components of Innate Immune
response
• Barriers
– Mechanical
– Chemical
– microbiological

• Soluble factors
– Cytokines and APP secreted by cells
– Responsible for cell activation and inducing inflammation

• Cells
– Intra/ extracellular killing of pathogens
– Induce inflammation
• All these act differently but synergistically
 Mechanical barriers

- Intact skin
- Mucous coat
- Mucous secretion
- Blinking reflex and tears
- The hair at the nares
- Coughing and sneezing reflex
 Chemical barriers
- Sweat and sebaceous secretion

- Hydrolytic enzymes in saliva

- HCl of the stomach

- Proteolytic enzyme in small intestine

- Lysozyme in tears

- Acidic pH in the adult vagina

 Microbiological barrier
Normal bacterial flora

- Competition for essential nutrients

- Production of inhibitory substances

 Cells
1. Natural killer (NK) cells
• Large granular lymphocytes

• Function :
– Cytotoxic for viral infected cells and tumor cells
– Secrete perforins which makes punctures in target cells
– Responsible for antibody–dependent cell mediated
cytotoxicity (ADCC)
 Cells ctd….
2. Phagocytes
• Specialized cells for capture, Ingestion and destruction of invading
microorganisms
a) Neutrophils (Polymorphoniclear leucocytes ): granulocytes circulate
in blood

b) Macrophages (Mononuclear cells )

- Monocytes in blood
- Histocytes in connective tissues
- Fixed reticuloendothelial cells in liver spleen, LN, BM
• Function : Phagocytosis
APC (Macrophages)
 Phagocytosis

• Steps
– Chemotaxix and attachment
– Engulfment and Phagosome formation
– Phagolysosome formation- Fusion with lysosomal
granules
– Killing Oxygen depended system
Oxygen-independent system
Phagocytosis
 Cells ctd…
Mast cells, Basophils and Eosinophils
• Mast cells- found throughout the body in connective tissues
• Basophils- found in circulating blood
• Eosnophils- in blood
• Upon stimulation they release granular contents (e.g. Histamine,
cytokines) and cause extracellular killing of pathogens

Dendritic cells
• Communicate b/w innate and adaptive systems
• Act as APC (Antigen Presenting cells)
• When activated by pathogens move to the lymphoid organs to
activate T cells
 Soluble factors

1- Acute phase proteins- (CRP=C reactive protein, Fibrin etc.)

2- Complement (proteins in serum, body fluids)
2- Interferons (Proteins against viral infections)
3- Properdin (Complement activation)
4- Beta lysine (Antibacterial protein from Platelets)
5- Lactoferrin,Transferrin (Iron binding protein)
6- Lactoperoxidase (Saliva & Milk)
7- Lysozyme (Hydrolyze cell wall)
 Phases of immune response
• Recognition
• Activation
• Elimination (effector phase)
Recognition by Innate Immune System
• Microbes evolve rapidly, so innate immunity must focus on
broadly expressed molecules shared by broad groups of
microbes (“pathogen-associated molecular patterns” - PAMPs)
e.g. – bacterial/viral DNA/ RNA, LPS, teichoic acid

• These are not present on host cells ( only on pathogens)

• They are essential for survival, so are conserved (cannot get

mutated)

• Cells of innate system have receptors to identify PAMPs called

“pattern recognition receptors”
• E.g. Manose receptors, Toll like receptors, Scavenger receptors
Toll-like receptors and recognition of
pathogens
 Activation and Effector Phase
Recognition

Activation

Effectors (Elimination)

Phagocytosis Extra-cellular Secretions (CKs & APP)

killing
Inflammation
Phagocytosis
 Inflammation
Inflammatory response

Tissue damage
Release of chemical mediators from Leukocytes
(Histamine, fibrin, kinins, cytokines) Invading microbe

Redness of tissue
Tissue temperature
Vasodilatation of capillaries Capillary permeability
Influx of fluids
Influx of phagocytes
into tissues
 Extracellular killing
• NK cells
– Secrete perforins and granzymes
– Also ADCC
• Eosinophils
– Secrete granular contents
– Important against larger parasites
 SDL
• ADCC
• Functions of different types of innate cells
• Function of antigen presenting cell (APC)
• Role of innate immune response in directing
adaptive immune response
 Summary
Immune response

Innate Acquired

Barriers 1)Prevent entry

Cells 2) Extracelular killing by NK cells, eosino, baso
Soluble factors 3) Intracellular killing (phagocytosis) by neutro,
macro
4) Inflammation induced by soluble mediators