Immunity

2.  Major Histocompatibility Complex
 MHC Act As Antigen Presenting Structures
 In Human MHC Is Found On Chromosome 6
› Referred to as HLA complex

3. • The products of the MHC play a
fundamental role in regulating immune
responses
• T cells must recognise antigen as a
complex with MHC molecules
• This requires antigen to be processed by
unfolding and proteolytic digestion before it
complexes with the MHC molecule

4. › It plays role in discriminating
self/non-self
› Participant in both humoral and cell-
mediated immunity
› Once formed the complex of
antigenic peptide and MHC are
generally very stable (half life ~
24hrs)

5. • MHC class I molecules are widely
expressed, though the level varies between
different cell types
• MHC class II molecules are constitutively
expressed only by certain cells involved in
immune responses

6.  Genes Of MHC Organized In 3 Classes
› Class I MHC genes
 Glycoproteins expressed on all nucleated cells
 Major function to present processed Ags to TC
› Class II MHC genes
 Glycoproteins expressed on B-cells, DCs
 Major function to present processed Ags to TH
› Class III MHC genes
 Products that include secreted proteins that have
immune functions. Ex. Complement system,
inflammatory molecules

7. • Class I MHC Genes Found In Regions A, B
and C
• Class II MHC Genes Found In Regions DR,
DP and DQ
• Class I and Class II MHC Share Structural
Features
– Both involved in APC
• Class III MHC Have No Structural Similarity
To Class I and II
– Ex. TNF, heat shock proteins, complement
components
Class I, II and III MHC

9. • biological role of MHC proteins is to bind
small peptides and to "present" these at the
cell surface for the inspection of T cell
antigen receptors
• The allelic variation of MHC molecules is
functionally reflected in the selection of
peptides which can bind

10. • T cells requires MHC antigens

11. • The 2 classes of MHC molecule are specialised
to present different sources of antigen
• MHC class I molecules present endogenously
synthesised antigens, e.g. viral proteins
• MHC class II molecules present exogenously
derived proteins, e.g. bacterial products or
viral capsid proteins

12.  First response to particular antigen called
primary response
› May take a week or more to develop
 Immune system remembers pathogen on
subsequent exposure
› Termed secondary response
 Adaptive immunity divided into
› Humoral immunity
 Eliminates extracellular pathogens
› Cellular immunity
 Eliminates intracellular pathogens

13.  Overview of humoral immunity
› Mediated by B lymphocytes
 a.k.a B cells
› Develops in bone marrow
› B cells may be triggered to proliferate into plasma
cells
 Plasma cells produce antibodies
 Antibodies produce when antigen bonds B cell receptor
› Some B cells produce memory cells

15.  Overview of cellular immunity
› Mediated by T lymphocytes
 a.k.a T cells
› Matures in thymus
› Divided into 2 subsets
 Cytotoxic T cells
 Helper T cells
 T cell receptors help with antigen recognition

16.  Coined from compounds that elicit antibody
production
› Antibody generator
 Includes an enormous variety of materials
 Today, term used to describe any compound
that elicits an immune response
› Antigen that causes immune response termed
immunogen
 Proteins and polysaccharides induce string
response
› Lipids and nucleic acids often do not
 Recognition of antigen directed at antigenic
determinant or epitope

17.  Structure of the Antibody (Ab)
› Basic Y-shaped structure
› Made of four chains of amino acids held together by disulfide bonds
 Two chains are heavy
 Two chains are light
› Each heavy and light chain has a constant region
 The constant region is known as Fc region
› Each heavy and light chain has a variable region
 Variable region is unique to each Ab
 This region binds to a specific Antigen and is known as “Fab” region

18.  Protective outcomes of
antibody-antigen binding
› Neutralization
 Prevents toxin from interacting with
cell
› Immobilization and prevention
of adherence
 Antibody bonding to cellular
structures to interfere with function
› Agglutination and precipitation
 Clumping of bacterial cells by
specific antibody
 Bacteria more easily phagocytized

19.  Protective outcomes of
antibody-antigen binding
› Opsinization
 Coating of bacteria with antibody to
enhance phagocytosis
› Complement activation
 Antibody bonding triggers classical
pathway
› Antibody-dependent cellular
cytotoxicity
 Multiple antibodies bind a cell which
becomes target for certain cells

20.  Lymphocyte characteristics include
› Immature
 Antigen specific receptors not fully developed
› Naive
 Have antigen receptor but have not encountered antigen
› Activated
 Able to proliferate
 Have bound antigen
› Effectors
 Descendents of activated lymphocytes
 Able to produce specific cytokines
 Plasma cells, T helper and cytotoxic T cells effector cells
› Memory lymphocytes
 Long-lived descendents of activated lymphocytes
 Memory cells responsible for seed and effectiveness of
secondary response
 Remembers antigen on subsequent exposure

21.  General characteristics
› Two major function T cell populations
 Cytotoxic T cells
 Proliferate and differentiate to destroy infected or
cancerous “self” cells
 Have CD8 marker
 Recognize MHC class I
 Helper T cells
 Multiply and develop into cells that activate B cells and
macrophages
 Stimulate other T cells; orchestrate immune response
 Have CD4 marker
 Recognize antigen display by MHC class II

22.  Functions of Tc (CD8) cells
› Induce apoptosis in “self” cells
 Cells infected with virus or intracellular
microbe
 Destroys cancerous “self” cells
› Nucleated cells degrade portion of
proteins
 Load peptides into groove of MHC class I
molecule
 MHC class I molecule recognized by
circulating Tc cell
 Cell destroyed by lethal effector function of
Tc cell
 Tc cells releases pre-formed cytokines to
destroy cell

23.  Functions of TH (CD4) cells
› Orchestrate immune response
 Recognize antigen presented by MHC class II
molecules
 MHC class II molecules found only on APC
 If TH cell recognizes antigen, cytokines are delivered
 Cytokines activate APC to destroy antigen

24.  Role of TH cells in B cell activation
› If TH cell encounters B cell bearing peptide: MHC
calls II complex
 TH cell responds by producing cytokines
› B cell is activated in response to cytokine
stimulation
 B cell proliferates and undergoes class switching
 Also drives formation of B memory cells

25.  Role of TH cells in macrophage
activation
› Macrophages routinely engulf
invading microbes resistant to
lysosomal killing
› TH cells recognize macrophage
with engulfed microbes resistant
to killing
› TH cells activate macrophages by
delivering cytokines that induce
more potent destructive
mechanisms