Topic 9 Immune responses

Question 1

What typical properties do the innate immunity have?

Answer 1

It’s fast and have a non-specific defense and response to injury

Question 2

What comprises the innate immunity?

Answer 2

Epithelial barriers (skin, mucous), acidic environment&enzymes, phagocytes, Natural killer (NK) cells, proteins & enzymes that lyse or inactivate bacteria (complement factors)

Question 3

Which cells are the phagocytes?

Answer 3

Dendritic cells, macrophages and neutrophils

Question 4

Whats the role of NK cells?

Answer 4

They sense virus infected cells and lyse them

Question 5

Whats the role of cytokines?

Answer 5

They activate macrophages, neutrophils, NK cells and enhance microbial killing

Question 6

What are the 3 main functions of the complement proteins?

Answer 6

1. C3b bind. to foreign surfaces - induce phagocytosis.
2. Cleaved C3b into C5a & C3a recruits and activate leukocytes that kill the microbes
3. Can form the membrane attack complex (MAC)

Question 7

What’s the classical pathway?

Answer 7

Antigen-antibody binding result in C1 binding to constant portion of antibody, cleaving into a and b fragments, followed by formation of C3 convertase and C5 convertase. Ends in formation of the Membrane Attack Complex (MAC) that inserts itself as a pore into foreign cells, causing lysis.

Question 8

What’s the alternative pathway?

Answer 8

Starts when C3 spontaneously hydrolyses and C3b binds to a surface (if host cell = rapidly deactivated). Involves factor B and D. Formation of C3 convertase, C5 convertase and resulting in formation of Membrane Attack Complex (MAC)

Question 9

Where is the Complement 3 usually found?

Answer 9

C3 is usually found in blood plasma/serum

Question 10

What does both the alternative and classical pathway result in?

Answer 10

Membrane Attack Complex (MAC) formation that creates a hole in the membrane to kill the cell via osmotic lysis

Question 11

Name some links between the inflammatory process and the complement system

Answer 11

• C1 and C3 can be activated by plasmin & Kallikrein or other by-products from coagulation
• C3-5a can activate leukocytes
• C5a chemoattractant for neutrophils and macrophages
• C3b opsonization -> recognition for phagocytes

Question 12

Further explain the opsonization process

Answer 12

Bacteria are “opsonized” by the binding of an antibody and C3b to receptors on the phagocyte membrane - which then stimulates phagocytosis. The complex of the antibody and C3b is called opsonin.

Question 13

How does the complement react to biomaterials?

Answer 13

Surface reaction then through the alternative pathway by C3b binding and through the classical by IgG binding and activating C1. (IgG is the most common AB)

Question 14

Which two enzymes are needed for the complement to create the MAC?

Answer 14

First C3 convertase enzymes then C5 convertase enzymes.

Question 15

How is the complement activation regulated?

Answer 15

Short half-life of the enzymes in the cascade. Regulatory proteins called “regulator of complement activation” (RCA) proteins

Question 16

How can complement activation be controlled at the biomaterial surface?

Answer 16

1. Limit the C3b deposition (reduced amount of nucleophiles at surface)
2. Immobilize RCA proteins at surface
3. Induce C5a binding to surface by negative surface groups

Question 17

What typical properties do the adaptive immunity have?

Answer 17

Specific defense against individual foreign stimuli. Long-term. Cell-mediated immunity (cytotoxic activity of T cells) and humural immunity (prod. of antibodies by B cells)

Question 18

What is histocompatibility?

Answer 18

Each individual expresses many unique HLA proteins on the surface of their cells, which signal to the immune system whether a cell is part of the self or an invading organism.

Question 19

What are MHC/HLA proteins?

Answer 19

Major histocompatibility complex in humans are the human leukocyte antigens (HLA)

Question 20

What’s the main function of MHC proteins?

Answer 20

The main function of MHC proteins are to bind to antigens derived from pathogens and display them on the cell surface for recognition by the appropriate T-cells.

Question 21

What’s the difference between MHC class I and II?

Answer 21

Class I MHC molecules have β2 subunits so can only be recognised by CD8 co-receptors. Class II MHC molecules have β1 and β2 subunits and can be recognised by CD4 co-receptors. In this way MHC molecules decide which type of lymphocytes may bind to the given antigen with high affinity, since different lymphocytes express different T-Cell Receptor (TCR) co-receptors.

Class II: “come and do something!” to T helper cells
Class I: “come and kill me!” to T cytotoxic cells

Question 22

What’s cluster of differentiation (CD)?

Answer 22

surface molecules used for immunophenotyping cells as they have different CD proteins expressed at different stages of maturation or differentiation. E.g. helper T cells are CD4 positive. These CD often act as receptors.

Question 23

Briefly describe the stages of cell-mediated immunity

Answer 23

A T helper binds to the APC presenting the antigen. It can then activate cytotoxic T cells that kill cells displaying the antigen. The helper and cytotoxic T cells also clone themselves into memory cells. They also activates B cells that also clone into memory cell and also differentiate into plasma cell secreting antibodies.

Question 24

What’s the role of APCs?

Answer 24

APCs, or antigen presenting cells, endocytose foreign material/bacteria/viruses, then move to the lymph nodes where the APC presents antigen peptides.

Question 25

What is an antibody?

Answer 25

A immunoglobulin with glycoproteins that can bind to specific epitopes on antigens. There exists different classes but the IgG is the most common.

Question 26

What are the main roles of antibodies?

Answer 26

1. Neutralization and lysis of microbes and toxins
2. Opsonization for phagocytosis
3. antibody-dependent cellular cytotoxicity
4. Inflammation/complement activation

Question 27

What’s a hypersensitivity reaction?

Answer 27

When something normal is recognized as something foreign - allergic reaction. small molecues/ions act as haptens which complex with proteins to activate the T cells - become a inflammation.