Congenital immunodeficiencies

what are immunodeficiencies

Defects in the development and functions of immune system that result in increased susceptibility to infections and some cancers

Immunodeficiency diseases

disorders caused by defective immunity

congenital immunodeficiencies

primary immunodeficiencies from genetic abnormalities

where do some other immunodeficiencies come from

infections, nutritional abnormalities, medical treatments that cause loss or inadequate function

how common are congential immune deficiencies

1 out of 500 individuals

What the genetic defects of congential immune deficiencies lead to

Impaired maturation of immune cells and impaired function of immune components

Which chromosome is normally linked to congential immundeficiencies

X-linked. Females are most likely carriers and males are more affected

What can a complete loss of function mutation and hypomorphic mutation do

complete loss of function: leads to one disease state

Hypomorphic: only partial loss of function

What are the 3 ways congenital immunodeficiencies can appear

X-linked, more in males than in females

Complete loss of function mutations

mutations in certain genes that can lead to one being susceptible to specific pathogens

what two abnormalities in innate immunity can cause immunodeficiency

phagocytes and complement system

Examples of diseases caused by innate immunity problems

Chronic granulomatous disesase

leukocyte adhesion deficiency

chediak higashi syndrome

defects in lymphocyte maturation

defects in lymphocyte activation and function

chediak higashi syndrome

lysosomal granules of leukocytes and NK cells don’t work right

Chronic granulomatous disease

caused by mutations in genes for enzyme phagocyte NADPH oxidase = it doesn’t work right so it doesn’t kill right. causes immune system to send for more macrophages, and the excess creates a granuloma

Leukocyte adhesion deficiency

deficiencies of almost every complement protein and genes incorrectly encoding for integrins

what do defects in lymphocyte maturation mean

genetic abnormalities causing a block in maturation of b and t lymphocytes

what do defects in Lymphocyte Activation and Function

they don’t work right. Defective antibody production, and bad b-cells. caused by X chromosome mutations

what’s common variable immunodeficiency (CVID)

Heterogeneous group of disorders that are characterized by poor Ab responses to infections and reduced serum levels of IgG and IgA

Inherited abnormalities that interfere with t-cell activation

Bare lymphocyte syndrome, hemophagocytic lymphohistiocytosis

what is bare lymphocyte syndrome

Caused by failure to express class II MHC molecules from mutations in transcription factors that normally induce class II MHC expression > No recognition of Ags by CD4+ T cells so no activation of T-cells

Hemophagocytic lymphohistiocytosis (HLH) syndromes

Genetic disorders in which cytotoxic CD8+ T cells and NK cells are unable to kill virus-infected target cells

mutations to the gene encoding perforin and granule exocytosis

what are some treatments for congenital immundeficiencies

Hematopoietic stem cell transplantation, IV injections of pooled immunoglobulin

IV injections of pooled immunoglobulin

passive immunity is given to patient from donors, really useful for agammaglobulinemia

What therapy is used for selective b-cell defects

IV injections of pooled immunoglobulin

what is hematopoietic stem cell transplantation used for

Severe Combined Immunodeficiency Disease (SCID)

What are acquired secondary immunodeficiencies

Deficiencies of the immune system that are acquired during life

What’s a really serious acquired immunodeficiency syndrome

AIDS

What’s HIV

a retrovirus infecting cd4+ t-cells and causes progressive destruction of said cells

What is the pathogenesis of aids

Starts off as HIV for a few years then HIV production leads to death of infected cells as well as to death of uninfected lymphocytes and subsequently immune deficiencies and clinical AIDS

Acute HIV syndrome

Early after HIV infection > mild acute illness with fever and malaise with initial viremia > subsides within a few days (clinical latency)

latency period of hiv

progressive loss of CD4+ T cells in the lymphoid

tissues and some destruction of these lymphoid tissues

 Blood CD4+ T cell count begins to decline

 Blood count falling to below 200 cells/mm (normal is 1500)

 Patient becoming susceptible to infections

clinical aids

increased susceptibility to infections and some cancers because of the immune deficiency. normally killed by an oppurtunistic pathogen