PL 4.2 Complement System and MHC Antigens

F; Heat-labile
T
F; Exit as proenzymes
T

MTF: Characteristics of the complement System

1.) Complex series of Heat-stable proteins
2.) Bind with Ab to eliminate antigens and is not antigen-spefific
3.) Exist in their active form
4.) Constitutive and needs to be activated

Liver

Where are the complement system proteins mainly produced?

Opsonization, Cell Lysis, Chemotaxis, Increased vascular permeability, and Mast cell degranulation

5 functions of the complement system

Opsonization

This function of the complement system makes pathogens more susceptible to phagocytosis

Cell Lysis

This function of the complement system allows it to directly destroy and eliminate pathogens

Chemotaxis

This function of the complement system allows it to produce substances that attract neutrophils and macrophages

Microbial cell surface

Where does the activation of the complement system occur

Antibody on the surface and Polysaccharides on microbial cell surface

2 triggers for complement system activation

Hydrolysis

Activation of a complement system involves what biochemical process

B fragment

This is the major fragment of the complement protein that has 2 biological active sites

A fragment

This is the major fragment of the complement protein that is released in the fluid phase to contribute to the inflammatory response

1 for binding to cell membrane of pathogen, 1 for cleavage of next complement protein

What are the functions of the 2 biological active sites of the major fragment

Convertase

This is the complement enzyme the converts an inactive complement protein into an active one

Activation of C3 convertase, C5 convertase, and formation of MAC

3 major steps of the complement system

C3

This is the keypoint for both the classical and alternate pathway

Internal Thioester bond between glutamine-COOH and cysteine-SH

This bond is cleaved during the hydrolysis of C3 protein

Proteolytic cleavage via C3 convertase and Spontaneous Hydrolysis of C3

2 mechanisms for cleavage of C3

Ag-Ab complex

What induces the classical pathway of complement activation

Microorganisms

What induces the alternative pathway of complement activation

C1q, C1r, C1s

This is the recognition unit of the classical pathway

C2, C3, C4

This is the activation unit of the classical pathway

Ca2+

The cohesion of the recognition unit of the classical pathway is dependent on what molecule?

C1q

This is the actual recognition unit of the classical pathway that allows for binding of Ig-Fc

C1 esterase

Activation of the recognition unit leads to the generation of what enzyme?

C2 and C4

C1 esterase cleaves what complement proteins?

F; Other way around

T/F: C2 will be cleaved first then C4

T

T/F: C4a is released while C4b remains bound to cell membrane

F; C2b is now the smaller fragment

T/F: C2a is released while C2b remains bound to cell membrane

C4b2a

C3 convertase of the classical pathway

C4b2a3b

C5 convertase of the classical pathway

F; It can cleave up to 1000

T/F: 1 molecule of C3 convertase can only cleave 1 C3 molecule

Spontaneous Hydrolysis

This mechanism of C3 cleavage fuels the alternate pathway

Factor B

What factor binds to C3 in the alternate pathway

Factor D

What factor cleaves Factor B into Ba and Bb in the alternate pathway

C3bBb

C3 convertase of the of the alternate pathway

Factor P

This factor stabilizes the C3 convertase in the alternate pathway

C3bBb3b

C5 convertase of the alternate pathway

MASP-2

Which part of the MBL is activated and cleaves C4 and C2

C5b67

This MAC complex is hydrophobic and inserts into the lipid bilayer

C5b6789

This MAC complex is the final lytic plug molecule

C1 inhibitor

This molecule inactivates C1r and C1s which prevents the formation of C3 convertase IN THE CLASSICAL PATHWAY

Protein H

This molecule prevents binding of the factor B to membrane-bound C3b preventing formation of C3 convertase IN THE ALTERNATE PATHWAY

Factor I

This molecule cleave C3b into C3c and C3d which are inactive

MAC inhibitory protein, Homologous Restriction Factor, and Protein S (Vitronectin)

The final lytic pathway is regulated by what 3 molecules?

MHCs

These function in lymphocyte recognition and antigen presentation

Transplantation antigens

These are antigens monitored in donor and recipient tissue in transplantation

BCA Region

Encoding region on Class I MHCs

Chromosome 6

MHC Classes are encoded by 75 genes on what chromosome?

D Region

Encoding region on Class II MHCs

Between BCA and D region

Encoding region on Class III MHCs

T
F; Constant not variable
T
F; It is non-covalently bound

MTF: Structure of Class I MHCs

1.) Variable alpha chain
2.) Variable beta2 macroglobulin chain
3.) Groove between alpha 1 and 2 domains
4.) alpha 3 domain is covalently bound to the beta chain

Between alpha1 and beta1 domains

Where is the groove found int Class II MHCs

HLA-A, HLA-B, HLA-C

3 MHC I Groups

HLA-DP, HLA-DQ, HLA-DR

3 MHC II Groups

Class I

This MHC class is found in virtually every cell

Class II

This MHC class is found mainly in antigen-presenting cells

Cytotoxic T cells

Target for presenting antigens in Class I MHCs

Helper T Cells

Target for presenting antigens in Class II MHCs

Endogenous antigens (Viral or Tumor proteins)

Type of antigen presented in Class I MHCs

Exogenous antigens (Bacterial cells or viruses)

Type of antigen presented in Class II MHCs