Lecture 16: Failures of the Bodys Defenses

serotypes

strains of a bacterium

Describe how having multiple serotypes allows a pathogen to avoid the immune response

• there are many serotypes (aka strains) on a bacterium that have different surface polysaccharides

• if a host makes an antibody agasint serotype 1 it will not protect from serotype two, leading toanother primary immune response

antigenetic drift

accumulation of point mutations that alter surface antigens

effect of antigenetic drift in the human population

as the virus spreads from person to person the RNA is altered slightly which may cause neutralizing antibodies previously made against the virus to be ineffective

antigenetic shift

recombination of viral RNA that results in new viral variants, given rise by a secondary host being infected with two strains from two different species that recombine to produce a novel virus

effect of antigenetic shift in the human population

movement into the human population can cause a pandemic since there is no crossprotective immunity

VSG

variable surface glycoproteins

how T. brucei uses VSG

thousands of VSG are excised and cycle through expression to avoid protective immunity, giving rise to chronic cycling and deposition of immune complexes and inflammation that leads to neurological damage and coma

chronic cycling

T. brucei expresses dominant VSG, when taken care of by the immune system the minority VSG then becomes dominant

how S. typhimurium escapes immune response

can invert its DNA segment to alternate flagellin to avoid protection (TLR 5 recognizes flagellin)

how N. gonorrhoeae escapes immune response

pillin protein is encoded by variant genes expressed one at a time

hiding in latency

such as Herpes simplex, the infection is cleared but the virus hides where it cannot be found and can layer re-emerge when advantageous to do so

superantigens

molecules that bind non-specifically to TCR and MHC which activates T cells in absence of antigen, resulting in massive stimulation of T cells which gives rise to cytokine production and systemic shock

immunodeficiency (ID) disease

an inherited or acquired disorder in which some part of the immune system is absent or defective, resulting in failure to mount and effective immune response

three primary types of ID diseases

◦ dominant: 1 defective allele and one normal allele

◦ recessive: 2 defective alleles

◦ X-linked: recessive defect in gene on X chromosome

AIDS vs HIV

HIV causes AIDS

HIV life cycle

1. HIV gp120 binds CD4 on host T cell

2. gp41 helps viral membrane fuse with host membrane

3. viral core released into cytoplasm, RNA is reverse transcribed to cDNA (complement DNA)

4. integrate inserts cDNA into host cell genome -> now a provirus

5. low level transcription of provirus occurs during T cell activation

6. synthesis of Rev and Tat (proteins)

7. Rev and Tat produce viral particles

8. new viral particles bud

T cells vs HIV viral load

less CD4 T cells = increased viral load

how many T cells to classify AIDS?

<200

HAART

• combines therapies to target elimination of viral variants

• it reduces the viral load by preventing new infections, but does not stop viral production in infected cells

role of opportunistic infections with HIV

parasites, bacteria, fungi or viruses that take advantage of a compromised immune system

three mechanisms of cell death with HIV

1. direct killing by lysis

2. increases susceptibility to apoptosis

3. CTL killing

purpose of a bone marrow transplant

reconstitute a patients hemopoietic system with healthy hemopoietic stem cells (HSCs)

two functions of HLA matching

1. Reduces effects of grafts vs host disease (GVHD)

2. ensures effective reconstitution of adaptive immune response

IL-12R: deficiency and outcome

• deficiency: IL-12R (binding here eventually leads to macrophage activation)

• outcome: no macrophages activation, persistent intracellular infections

XLA: deficiency and outcome

• deficiency: kinase Btk (aids in BCR signaling and growth of pre-B cells

• outcome: no signaling via pre-BCR, B cells arrested at pre-B cell stage

HANE: deficiency and outcome

• deficiency: CI INH (inhibitor of C1 and Cs protease activity)

• outcome: overstimulation of complement and edema

CGD: deficiency and outcome

• deficiency: NADPH oxidase (makes reactive oxygen species)

• outcome: failed respiratory burst, chronic infection, granuloma formation

SCID (via ADA): deficiency and outcome

• deficiency: adenosine deaminase (ADA) (breaks down toxic metabolites)

• outcome: no macrophage activation, persistent intracellular infections