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Innate Immunity

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4 views

Innate Immunity

Uploaded by

Kavya
Copyright
© © All Rights Reserved
Available Formats
Download as PPTX, PDF, TXT or read online on Scribd
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Normal Immune Response

• Immunity: The classic definition is protection from infectious pathogens

• Immunity in broader sense includes:


• host reactions against cancers (tumor immunity),
• tissue transplants,
• and even self antigens (autoimmunity).

• Falls into two categories:


- Innate Immunity: Natural or native immunity

- Adaptive Immunity: Acquired or specific immunity


• Physical barriers: Skin and mucosal barriers - keep hazardous materials outside
the body
• Phagocytes: neutrophils and macrophages: engulf pathogens and cell debris

• Immunological Surveillance: natural killer cells (NK cells) destroy abnormal


cells.
• Interferons: Chemical messengers that coordinate the defenses against viral
infections. Antiviral proteins do not kill viruses but block
replication in cell

• Complement: Complement action of antibodies to destroy pathogens


• Inflammation: Triggers a complex inflammatory response limiting the spread
of infection
• Fever: A high body temperature which increases body metabolism, and accelerates
body defense
The major functions of immune system are as under:

i) Recognition of self from non-self


ii) Mounting a specific response against non-self
iii) Memory of what was earlier recognised as non-self
iv) Antibody formation
v) Cell-mediated reactions
Innate Immunity

• First line of defense

• Intrinsic mechanisms that are poised to react immediately

• mediated by cells and molecules that recognize products of microbes and dead
cells and induce rapid protective host reactions
Components of innate immunity
Major components include:

- Epithelial barriers that block entry of microbes


- Phagocytic cells (mainly neutrophils and macrophages)
- dendritic cells
- natural killer cells
- other innate lymphoid cells
- several plasma proteins including proteins of complement system
• Epithelium of skin, gastrointestinal tract and respiratory tract act as barriers to the
entry of microbes

• Epithelium produces antimicrobial molecules such as defensins and lymphocytes


located in the epithelium to combat microbes

• Monocytes and neutrophils are phagocytes in the blood that can be rapidly
recruited to any site of infection

• Tissue resident macrophages: Kupffer cells in liver, microglia in brain and


alveolar macrophages in lungs
• Dendritic cells are specialized cells present in epithelium, lymphoid organs

• They capture protein antigens and display peptides for recognition by T cells (Ag
presenting cells)

• DCs have rich collection of receptors that sense microbes and damaged cells and
stimulate secretion of cytokines

• DCs serve as sentinels that detect danger and initiate immune response
Innate lymphoid cells
• Are the tissue resident lymphocytes that lack T cell antigen receptors

• Can’t respond to antigens


• Instead are activated by cytokines and other mediators produced at the site of
tissue damage

• Innate lymphoid cells are classified into group 1, 2, 3 based on the dominant
cytokines they produce. They produce same cytokines as Th1, Th2 and Th17
subsets of CD4

• NK cells provide protection against viruses and intracellular bacteria


• Mast cells: capable of producing many mediators of inflammation

• Plasma proteins: Several soluble proteins play role in innate immunity

• Complement system: Plasma proteins that are activated by microbes


• Innate immunity has two components

• Humoral: comprised of complement

• Cellular: consists of neutrophils, macrophages and NK cells


Cellular receptors for microbes, products of damaged cells
and foreign substances
• Cells that participate in innate immunity are capable of recognizing certain
components that are shared among related microbes

• Microbial structures that are recognized by innate cells are: Pathogen associated
molecular patterns

• Leukocytes recognize molecules released by injured or damaged cells: Damage


associated molecular patterns
• Pattern recognition receptors are located in all cellular compartments

• Plasma membrane receptors detect extracellular microbes

• Endosomal receptors detect ingested microbes

• Cytosolic receptors detect microbes in cytoplasm


• Toll like receptors: Essential for host defense against microbe
• Mammals have 10 TLRs, each recognizing a different set of microbial molecules

• TLRs are present in plasma membrane and endosomal vesicles

• All TLRs signal by a common pathway that culminate in the activation of two
transcription factors:

• NF-κB- Stimulates the secretion of cytokines and expression of adhesion


molecules- critical for recruitment of leukocytes
• Interferon regulatory factors (IRF): Stimulate production of anti viral cytokines
NOD-like receptor and the inflammasome
• NLR are cytosolic receptors

• Recognize a wide range of substances: products of necrotic or damaged cells, loss


of intracellular K+ ions

• These signal via cytosolic multiprotein complex called inflammasome


• It activates an enzyme caspase 1 that cleaves a precursor form of cytokine IL-1 to
generate biologically active form

• IL 1 is a mediator of inflammation that recruits leukocytes and induces fever.

• Gain of function mutation in NLR: autoinflammatory syndrome


• C-type lectin receptor (CLRs) expressed on plasma membrane of macrophages
and dendritic cells detect fungal glycans and elicit inflammatory reaction to fungi.

• RIG like receptors are located in the cytosol and detect nucleic acids of viruses
that replicate in the cytoplasm of infected cells

• These receptors stimulate the production of anti-viral cytokine


NK Cell
• The function of NK cell is to recognize and destroy severely stressed or abnormal
cells- virus infected cells and tumor cells

• NK cells make up 5-10% of peripheral blood lymphocytes

• NK cells express CD 16, a receptor for IgG Fc tail that confers NK cell the ability
to lyse IgG-coated target cells

• This phenomenon is called antibody dependent cellular cytotoxicity (ADCC)


Reactions of innate immunity
• Inflammation: Cytokines and products of complement activation are produced
during innate immune reaction

• These trigger vascular and cellular components of inflammation

• The recruited leukocytes destroy microbes and ingest and eliminate damaged cells

• Antiviral defense: Type 1 interferons produced in response to viruses on


infected/non-infected cells produce enzymes that degrade viral nucleic acids and
inhibit viral replication

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