L2: Adaptive immunity and MHC

Question 1

What are the types of adaptive immunity?

Answer 1

1) Humoral (Antibody - Mediated) Immunity.

2) Cell-Mediated Immunity.

Question 2

What is humoral immunity mediated by?

Answer 2

mediated by secreted antibodies

Question 3

What is the function of humoral immunity?

Answer 3

Its physiologic function is defense against extracellular microbes and microbial toxins

Question 4

What are the functions of antibody isotypes?

Answer 4

1) Neutralization of microbes and microbial toxins
2) Opsonization and phagocytosis
3) Antibody-dependent cell-mediated cytotoxicity (ADCC)
4) Activation of the complement by IgG and IgM “pathogen—> no reaction. Pathogen with AB —-> Reaction”
5) Functions of antibodies at special sites

Question 5

What is the naturalization function of microbes and microbial toxin by antibodies?

Answer 5

• Antibodies blocks and prevent binding of microbe to cells i.e. prevent infection of cells. “So that we don’t even need cell mediated immunity”
• Antibodies inhibit the spread of microbes from an infected cell to an adjacent cell.
• Antibodies block binding of toxin to cellular receptors, and thus inhibit pathologic effects of the toxin.

Question 6

What is the opsonization and phagocytosis function of antibodies?

Answer 6

Antibodies of IgG isotype opsonize (coat) microbes

Question 7

What is ADCC function of antibodies?

Answer 7

• IgG bind to infected cells by the Fab regions, and bind by Fc to Fc receptors on NK cells.
• The NK cells are activated and kill the cells.
• IgE “+IgG” bind to helminthic parasites by the Fab regions, and bind by Fc-to-Fc receptors on eosinophils.
• The eosinophils are activated to release their granule contents, which kill the parasites.

Question 8

What are the functions of antibodies at special sites?

Answer 8

Mucosal immunity

Neonatal immunity

Question 9

What is the function of antibodies in mucosal immunity?

Answer 9

• IgA is the major class that is produced by the mucosa-associated lymphoid tissues (MALT) in the GIT and RT and transported to the lumens of organs.
• In mucosal secretions, IgA binds to microbes and toxins present in the lumen and neutralize them by blocking their entry.

Question 10

What is the function of antibodies in neonatal immunity?

Answer 10

• neonates are protected from infection by maternal antibodies (IgG) “produced by mother” transported across the placenta into the fetal circulation and by antibodies in ingestd milk transported across the gut epithelium of newborns.

“But they are passive antibodies which last for six months”

“Newborns have good immunity to most infections that have have infected the mother”

Question 11

What are the characteristics of the primary immune response?

Answer 11

• When we are exposed to an antigen for the first time:

a) There is a lag of several days (10 days) before a specific antibody becomes detectable.
b) This antibody is IgM.
c) After a short time , the antibody level declines.

Question 12

What are the characteristics of the secondary immune response?

Answer 12

If at a later date we are re-exposed to the same antigen, there is

a) more rapid appearance of antibody, greater amount.
b) IgG class.
c) remains detectable for months or years.

Question 13

What happens if we are re-exposed to an antigen while we are exposed to a different antigen for the first time?

Answer 13

the properties of the specific response to this antigen are those of the primary response

Question 14

Compare between secondry response and primary response according to:-

Onset
Magnitude
Lifetime
Isotype

Answer 14

Onset: rapid - slow

Magnitude: High - low

Lifetime: long - short

Isotype: IgG (Or IgA, or IgE) - IgM

Question 15

Why does secondary immune response happen?

Answer 15

• because the immune system possesses specific immunologic memory for antigens.
• During the primary response, some B lymphocytes, become memory cells which are long lived.

Question 16

What phenomenon is required in the secondary response?

Answer 16

Thus we can see that the secondary response requires the phenomen known as class switching (IgM to IgG).

Question 17

What is the function of cell mediated immunity?

Answer 17

Eradicates infections by intracellular microbes.

Question 18

What are the steps of activation of cell mediated immunity?

Answer 18

• Consist of the activation of naïve T cells to proliferate and differentiate into effector cells (CD4+ T helper cells and CD8+ cytolytic cells; CTLs) and the elimination of the intracellular microbes

Question 19

What are the types of cell mediated immunity?

Answer 19

CD4+ T cells:

Differentiate into 2 effector cells according to cytokine production by antigen presentig cell:
 IL-12 leads to Th1
 IL-4 leads to Th2
 Th1 secrets IFN-g activates phagocytes to kill microbes.
 Th2 secrets IL-4 and IL-5 which stimulate eosinophil and mast cell degranulation in allergy and helminthic infection

CD8+ T cells:

kill any cell containing microbes or microbial proteins in the cytoplasm (intracellular) by direct cell cytotoxicity,; eliminating the reservoir of infection .

Question 20

How are T cells activated? “T-helper”

Answer 20

Activated by two signals
- The 1st signal: peptide + MHC on the surface of APCs recognized by TCRCD3.

• The 2nd co-stimulatory signal: is the interaction of B7 molecule on APCs with CD28 on T cells.

Question 21

What happens in case of absence of the second signal inactivation of T cells?

Answer 21

exposure of T cells to antigen lead to anergy (unresponsiveness)

Question 22

What are the steps of killing infected cells by CD8 - CTLs?

Answer 22

1) CTLs recognize class I MHC + peptides on the surface of infected “target” cell”.
2) Formation of tight adhesions “conjugates” with these cells.
3) CTLs are activated by IL-2 & IFN-γ to release their granule contents toward the target cell i.e. granule exocytosis.

4) The granules contents include:
- Perforin, which form pores in the target cell membrane
- Granzymes enter the target cells through these pores and induce apoptosis through the activation of caspases.

5) Detachment of CTL from target cells to kill other target cell.
6) Death of target cell.

Question 23

What is the definition of MHC?

Answer 23

• Group of genes on short arm of chromosome 6 which produce MHC molecules present on cell surfaces and responsible for display of protein Ag to T cell Also called human leucocytic Ag = HLA

Question 24

What is the classification of genes of MHC?

Answer 24

1) Class I MHC genes → HLA-A “human leucocytes antigen” & HLA-B & HLA-C → role in Ag presentation to Tc
2) Class II MHC genes → HLA-D region (HLA-DR & HLA-DP & HLADQ) → role in Ag presentation to Th
3) Class III MHC genes → lies between class I & II & not produce MHC but produce some complement components & TNF-α.

Question 25

What is the structure and distribution of MHC molecules?

Answer 25

- Are membrane proteins expressed on cells. - Each class I & II molecule consist of extracellular part, a transmembrane and a cytoplasmic part to anchore the molecule to the cell.

Question 26

What is the structure and function of class 1 MHC molecules?

Answer 26

- polypeptide chains, α chain formed of 3 domains (α1, α2, α3), attached to a polypeptide chain called β2 microglobulin encoded by a gene outside MHC. - α1 and α2 domains form the cleft or groove which bind peptide. - Present antigen to CD8+ cells. - Class I molecules are expressed on all nucleated cells.

Question 27

What is the structure and function of class 2 MHC molecules?

Answer 27

- 2 polypeptide chains α chain (α1 & α2) and β chain (β1 & β2). - α1 and β1 domains form the peptide binding cleft. - Present antigen to CD4+ cells. - Class II is expressed on APCs only.