lecture 8 - immunodeficiency

Question 1

What is an immunogen

Answer 1

Any substance that can induce an immune response

Question 2

Describe cytokine help

Answer 2

increased phagocytosis by macrophages, B cell antibodies enhance phagocytosis and neutralize pathogens

Question 3

Describe primary (congenic) immune deficiencies

Answer 3

Rare
Genetically determined
Diagnosed early in life
Involve innate or adaptive immunity

Question 4

Describe secondary (acquired) immune deficiencies

Answer 4

More common
Seen in patients with; malnutrition, infection, cancer, renal disease

Question 5

What are examples of innate immune deficiencies

Answer 5

TLR signalling
Leukocyte adhesion
Complement components
Phagolysosome function
Microbial activity

Question 6

Describe mutations in TLR signalling pathways

Answer 6

When TLRs mutated -> immune deficiency (quite restricted)
TLR3 defect - herpes simplex encephalitis (recognises dsRNS)

Question 7

Describe defects in leukocyte adhesion

Answer 7

LAD-1 & LAD-2 - impaired leukocyte adhesion and migration through endothelium
Defective phagocytosis
Defective generation of oxidative burst
LAD-1 - generally fatal in first yea of life
Succumb to bacterial infection
Rare

Question 8

Describe defects in phagolysosome formation
(Chediak-Higashi syndrome)

Answer 8

Lysosome/phagosome fusion results in pathogen destruction - impaired
Secretion of cytotoxic granules affected
Susceptible to bacteria/fungi and viral infection
Severe immunodeficiency (few live to teens - 200 worldwide)

Question 9

Describe defects in microbial activity (Chronic granulomatous disease)

Answer 9

genetic deficiency in ROS production
Oxygen dependent killing doesn’t occur
Microbes surrounded by activated macrophages causing granulomas
Recurrent, life-threatening bacterial and fungal infections

Question 10

Describe the effects of B cell deficiency

Answer 10

Increased susceptibility to pyogenic infections (educed opsonisation)
Impaired responses to bacterial toxins
Graft ejection and DTH normal
Poor antibody response with inactivated vaccines

Question 11

Describe the effects of T cell deficiency

Answer 11

Poor response to fungal, viral and intracellular bacteria
DTH responses poor
Prolonged graft survival

Question 12

Describe X-linked Agammaglobulinemia

Answer 12

More common primary immunodeficiency
Failure of pre-B cells - anti-B not formed properly
No plasma cells or immunoglobulin produced
Significant reduction in B cells in blood
Normal T cell responses
Recurrent bacterial infections - vial and protozoal infections

Question 13

Describe thymic hypoplasia (DiGeorge syndrome)

Answer 13

Deletion of 30-40 genes in chromosome 22
No thymus gland - no T cell development - very susceptible to infection
No T cell mediated response - no switching of antibody
High susceptibility to viral, fungal, protozoal and intracellular bacteria infection

Question 14

Describe Severe Combined Immunodeficiency Disorder (SCID)

Answer 14

Genetically distinct syndromes - affect humoral and cell mediated responses
- ADA deficiency (adenosine deaminase) - purine metabolism
Lack of enzymes cause accumulation of metabolites - toxic to lymphocytes
No B or T cells in patient

Question 15

How can you treat SCID

Answer 15

Bone marrow transplant at 3 months -
gene therapy development

Question 16

What are examples of secondary immune deficiencies

Answer 16

Autoimmune disease
Cancer
Accompanies measles, chicken pox, mumps, severe trauma leprosy, Hodgkin’s disease
Malnutrition
HIV-AIDS
therapy induced suppression of bone marrow or lymphocyte function

Question 17

Describe Human immunodeficiency virus (HIV)

Answer 17

infection via gp120 envelope glycoprotein of HIV RNA retrovirus binding to CD4 molecule
Low levels of CD4 on macrophages and dendritic cells
High levels of CD4 on T cells

Question 18

What are some HIV-associated diseases

Answer 18

Pneumocystis jiroveci (pneumonia causing fungus)
Recurrent mucosal candidiasis
Disseminated CMV
Severe herpes simplex
Disseminated mycobacterium
Toxoplasmosis of central nervous system