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I mmunity. BY GHADA FAWZY. Innate immunity. Definition: Non specific early line of defense , it is the first line ofdefense against infection. This prevent entery of micro-organisms, or they eliminate them prior to occurance of the disease. Elements of innate immunity.

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i mmunity

Immunity

BY

GHADA FAWZY

innate immunity
Innate immunity

Definition:

Non specific early line of defense , it is the first line ofdefense against infection. This prevent entery of micro-organisms, or they eliminate them prior to occurance of the disease

elements of innate immunity
Elements of innate immunity

Anatomical Cellular

Barriers components

Secretory Molecules

anatomical barriers
Anatomical barriers:
  • Skin: sweat, normal flora, intact skin.
  • Intestinal movements
  • Oscillation of bronco-pulmonary components
secretory molecules
Secretory molecules:
  • Organic acids&thiocyanate in saliva.
  • Low molecular weight fatty acids in GIT.
  • transferrin,lactoferrin,acute phase proteins,lysozymes,interferons,fibronectins, complements in serum
  • Interferons and tumor necrosis factor at site of inflammation.
slide7

Transferrin&lactoferrin deprive organism from iron.

  • Interferon inhibits viral replication& activates other cells to kill pathogens
  • Lysozyme breaks down bacterial cell wall.
  • Fibronectin coat(opsonize) bacteria rapid phagocytosis.
  • TNF viral replication & phagocytosis.
  • Complements direct &indirect (via phagocytic cells destruction of organisms
  • Acute phase proteins(CRP)+complement compat infection.
antimicrobial peptides
Antimicrobial peptides
  • Small molecular weight proteins with broad spectrum antimicrobial activity against viruses, bacteria&fungi
  • Types:

*Definsins:( α&β).

*cathelecidines.

*saposines

  • Function:

1- preserving normal epithelium by promoting epithelial growth&angiogenesis.

2- secreted by moist airway epithelium as biofilm

3- act as chemokines attract neutrophils,dendreticcells&Tlymphocytes

4- antimicrobial activity: desrupting membrane integrity of their victims&interact with negatively charged targets within the microbes

complements
COMPLEMENTS
  • A system of 20 glycoproteins circulating in blood &bathing in tissue fluids that share in both innate &adaptive immunity through:
  • The classical complement pathway. Activated by Ag-Ab complexes.
  • The lectin pathway activated by plasma lectins (mannose binding proteins) that bind to microbial carbohydrates.
  • The alternative pathway activated by C3b binding to microbial surface and to Ab molecules.

The end result is the production of a key enzyme (C3 convertase C3a&C3b , C4a, C5a.

function
Function:
  • Binds to the suface of the microbes (the phagocytic cells express Rs for C3b- opsonization) to enhance phagocytosis.
  • Chemotactically attract the phagocytes (esp. C5a).
  • Triggers inflammation (release of inflammatory mediators from mast cells &increase vascular permeability(C3a, C4a&C5a).
  • Cause lysis of G-ve bacteria & human cells displaying foreign epitopes.
  • Play role in activation of naive B cells.
  • Remove harmfull immune complexes from the body
cytokines
Cytokines:
  • Interferon: antiviral activity&inhibit Th2 cytokines.
  • Interleukins: exert effect on leucocytes. Inflammatory mediators(IL-1,IL-6,IL-8&TNF-α). Anti-inflammatory mediators(IL-10)
  • Chemokines: with chemoattractantactivity
  • TNF: induce MHC-II expression on keratinocytes
  • CAM(cellular adhesion molecules):

Surface glycoproteinswhich are important in the interaction of lymphocytes with APC, keratinocytes, endothelial cells and also in their trafficking in skin during inflammation

Eg.: Cadherins, Ig, integrin, selectins

toll like recptors tls
Toll like recptors(TLs)
  • A family of receptors that play important role in recognition of micobial components
  • TLR2 (lipoproteins&peptidoglycan), TLR4(lipopolysaccharides),TLR5(flagellin)
  • Dederitic cells express many TLRs- on activation- presnt antigen to naive T cells
cellular components
Cellular components
  • Neutrophils (PMN):
  • Azurophilic granules : cationic proteins, definsins, proteases, lysozymes esp. Myeloperoxidase.
  • Secondary granules: lysozymes, NADPH oxidase cofactors, lacto-ferrin&B-12 binding protein .
  • Mononuclear phagocytes:

monocytes&macrophages(have Rs for IgGFc, C, interferon, TNF and some bacterial componentsphagocytosis.

  • Eosinophils: Rs for IgEFccytotoxicity to parasites coated with IgE
  • Basophils: play role in immediate allergic reaction (anaphylaxis&angioedema)
  • Mast cells: type1 hypersensitivity reaction
natural killer cells nk
Natural killer cells(NK)
  • Resemble lymphocyte in morphology.
  • Participate in both innate &adaptive immunity
  • Concerned mainly in killing virus-infected cells&certain mutant cells

Target cell

Nk

STRESS INDUCED GLYCOPROTEIN

KILLER ACTIVATING RECEPTOR

+ + + +

- - - -

MHC1

KILLER INHIBITORY RECEPTOR

phagocyte response to infection
Phagocyte response to infection
  • At site of infection phagocytes can attach bacteria via:
  • Rs for bacterial polysaccharides(scavenger rs)
  • Host proteins that act as opsonins (fibronectin,C,IgG)
  • After attachment , phagosomeformation,activation of respiratory burst(hexosemonophosphate shunt)&production of super oxide anion,H2O2,NO (MICOBICIDAL SUBSTANCES)
adaptive immunity
Adaptive immunity
  • Antigen specific long term response mediated by lymphocytes&their products

Antigen: a substance that react with antibody or antigen receptors on lymphocytes.

Epitopes: the actual portion of antigen that react with antibodies or lymphocyte Rs.

- the epitope Rs on B lymphocyte (BCR- sIg)& on T lymphocytes (TCR)

Hapten: low molecular weight chemicals unable to provoke immune response unless they combine with protein

Superantigen: unusual bacterial toxins bind directly to outside of MHC-ІІ & activate large number of T4 lymphocytes

steps of adaptive immunity
STEPS OF ADAPTIVE IMMUNITY
  • Step 1: antigen must encounter APC & naive lymphocytes
  • Step 2: clonal selection (recognition of Ag epitopes by naive lymphocytes)
  • Step 3:clonal expansion (proliferation, differentiation of B-T4-T8 to exert successful immune response
  • Step 4:
  • B cells Igs
  • T4 Th1&Th2
  • T8 CytotoxicT lymphocytes(CTL)
  • Step 5:Formation of memory cells
slide19
T4

IL12

IL4

Th1 Th2

IL2,IFNδ,TNF --- IL2,4.5.10,13

cell mediated humoral

activate CTL,NK production of Igs

&macrophages &activate eoinophils

Th3: has suppressive effect on Th1&2

with production of IgE

mhc molecules
MHC molecules:

Antigens located on HLA gene on chromosome 6

1- MHC-I:

  • expressed on all nucleated cells
  • Can bind endogenous antigens (viruses, intracellular bacteria,tumor antigens)
  • MHC-I+bound peptide stimulate TCR-CD8 (CELL MEDIATED IMMUNITY)

2- MHC-II:

  • expressed on macrophages,B&T cells
  • Can bind exogenous antigens
  • MHC-II+bound peptide recognized by TCR-CD4(humoral&cell mediated)
antigen presenting cells apc
Antigen presenting cells(APC):
  • They capture & process antigen for presentation toTcells
  • They produce signals required for proliferation &differentiation of lymphocytes