Immunodeficiency Flashcards
______ is a process by which point mutations in viral genes cause alterations in structure of viral surface antigens; causes year-to-year antigenic variation.
Antigenic drift
Describe antigenic shift
- Virus reassorts its segmented genome and radically change surface antigen
- no one has immunity to it
- Usually the cause of influenza pandemics
______ are typically the cause of epidemics, whereas ______ are typically the cause of pandemics.
- Mutation; antigenic drift
- Recombination; antigenic shift
Why are RNA viruses more prone to error than DNA viruses? (Ex: influenza, HIV, coronaviruses)
RNA polymerase does not have the proof reading mechanisms that DNA polymerase has
________ is when a gene in the expression site is excised and replaced by a copy of a different homologous gene
Gene conversion
Viruses are cleared by ________ T-cells
Cytotoxic CD8 T-cells
Why are neurons good sites for latent viruses?
Neurons express small amounts of MHC I
______ viruses (3) infect epithelial cells and sensory neurons and remain latent in neurons. When reactivated, it travels down the sensory neuron to epithelium.
- Herpes simplex virus (HSV)
- Herpesvirus varicella-zoster (chicken pox/shingles)
- Epstein-Barr virus (EBV)
How does Mycobacterium tuberculosis evade the immune system?
- Prevents fusion of phagosome with a lysosome in macrophages
- Flourishes in vesicles
_______ evades the immune system by enclosing itself in an impenetrable membrane-enclosed vesicle that does not fuse with other vesicles, preventing antigen processing
Toxoplasma gondii
How does Treponema pallidum (syphilis) evade the immune system?
Coats itself with human proteins to evade antibody binding
______ expresses 10 proteins that prevent stimulation of NK-cells and CD8 T-cells; is life-threatening to immunocompromised individuals
Cytomegalovirus (CMV)
What medication is commonly used to treat CMV?
Acyclovir
_____ are small bacterial proteins that can crosslink MHCII on APCs or TCR on CD4 T-cells, causing nonspecific activation of CD4 T-cells and excessive production of IL-2, INF-γ, and TNF-α
Bacterial superantigens
Ex: Streptococcus aureus and Streptococcus pyogenes
Staphylococcal superantigen like protein 7 (SSLP7) prevents ________
- Monomeric IgA from delivering bacteria to phagocytes
- Contains binding sites for Fc region of IgA and C5 complement protein
What is the difference between primary and secondary immunodeficiency?
- Primary: inherited, causing enhanced susceptibility to infection or autoimmunity
- Secondary: due to environmental factors (immunosuppressive drugs)
Which type of gene causes immunodeficiencies in children? Dominant or recessive.
Dominant - only one allele is required, so it will be seen sooner
_____ activates macrophages and is produced by NK cells (innate), TH1 CD4 T-cells, and CD8 T-cells (adaptive)
IFN-γ
X-linked agammaglobulinemia (XLA) is caused by a defect in ______(protein) required for B-cell activation and pre-B-cell development and differentiation.
Bruton’s tyrosine kinase (BTK)
Why does XLA not occur in newborns until after 6 months of age?
- The newborn will still have some of the mother’s IgG
- Will begin to get recurrent bacterial infections
Phagocytosis defects lead to enhanced susceptibility to ________ infections
Bacterial
Identify syndrome:
- Mutation: CD18 subunit of CR3, CR4, and LFA-1 adhesion molecules
- Functional effect: Defective migration of monocytes and neutrophils to infected tissues; defective uptake of opsonized pathogens
- Clinical effect: widespread infection with encapsulated bacteria
Leukocyte adhesion deficiency (LAD)
Identify the syndrome:
- Mutation: NADPH oxidase
- Functional effect: Defective respiratory burst (release of ROS); Phagocytes unable to kill pathogens
- Clinical effect: Chronic bacterial and fungal infections; granulomas
Chronic granulomatous disease (CGD)
Identify the syndrome:
- Mutation: lysosomal trafficking regulator protein (LYST)
- Functional effect: Defective fusion of endosomes and lysosomes; defective phagocytosis
- Clinical effects: Recurrent and persistent bacterial infections; granulomas: damaging effects to many organs; partial albinism; peripheral neuropathy (nystagmus)
Chédiak-Higashi syndrome (CHS)
In LAD-1, what would you see in a peripheral blood smear?
- Neutrophilia
- Due to inability of phagocytes to exit circulation
What are the treatments for CGD?
- Lifelong regimens of antibiotics and antifungals
- IFN-γ treatment
- Hematopoietic stem cell transplant
What are the 3 P’s of CHS?
- Pyogenic infections (strep/staph)
- Partial albinism
- Peripheral neuropathy
Patients with CGD are susceptible to catalase-positive organisms (break down H2O2 and other ROS). What are some example organisms that someone with CGD would be susceptible to?
- S. aureus
- E. coli
- Pseudomonas
- Aspergillus
In the classical pathway of complement activation, C1-C4 are required for elimination of _______
Immune complexes
_______ deficiency results in accumulation of immune complexes in the blood and deposition of immune complexes in tissue
C1-C4
In the classical pathway of complement activation, ____ promotes the efficient elimination of bacteria by phagocytes
C3
______ deficiency results in increased susceptibility to encapsulated bacteria
C3
What is the function of C5-C9 in complement activation?
Formation of the membrane attack complex
C5-C9 deficiency results in increased susceptibility to _______
Neisseria infections
Hereditary angioedema is due to a deficiency ______, which leads to unchecked activation of complement components leading to decreased C2 and C4 protein.
C1 esterase inhibitor (C1INH)
How is hereditary angioedema inherited?
Autosomal dominant
Why does hereditary angioedema lead to airway obstruction and swelling of the eyelids, lips, tongue, genitals, hands, feet?
Bradykinin, the inflammatory mediator responsible for capillary leakage, is left unchecked due to the inability to eliminate C1.
How is hereditary angioedema treated?
- Danazol - synthetic androgen; promotes C4 synthesis and increases C1-INH
- Replacement therapy with C1-INH - for sudden attacks
What form of severe combined immunodeficiency (SCID) leads to impaired common gamma chains on cytokine receptors??
X-linked
What form of SCID is caused by an absence of adenosine deaminase (ADA) or purine nucleoside phosphorylase (PNP)?
Autosomal recessive
Which form of SCID is more common?
X-linked
In SCID that is X-linked, you will have mainly an absence of _____ cells, whereas in autosomal recessive you will have an absence of _____ cells.
- X-linked: T-cells
- Recessive: B-cells, T-cells, NK cells
SCID results in an extreme susceptibility to ____ infections
ALL infections
______ is a genetic abnormality caused by spontaneous deletion of a portion of chromosome 22, which prevents proper formation of the thymus (among other organs and structures)
DiGeorge syndrome
How is DiGeorge syndrome treated?
- Antibiotics for infections
- Calcium supplementation
- Ear tubes and/or hearing aids
- OT & PT
- Hormone replacement
- Surgery to repair heart defects, cleft palate, or nasal speech
_____ is an X-linked recessive disorder in the WASp gene, which plays a role in relaying extracellular signals to the actin cytoskeleton of hematopoietic cells.
Wiskott-Aldrich syndrome (WAS)
What are the symptoms of WAS?
- Recurrent bacterial infections
- Eczema
- Purpura
- Epistaxis
- Splenomegaly
In WAS, levels of Ig_ are low and Ig_ are elevated.
- IgM levels are low
- IgE and IgA are elevated
How is WAS treated?
Hematopoietic stem cell transplant (HSCT)
Hyper-IgM syndrome is characterized by and absence of _____ in the spleen and lymph nodes
germinal centers
Due to decreased levels of all other Ig in hyper-IgM syndrome, patients are more susceptible to ______ infections
Bacterial
Hyper-IgM is caused by a deficiency in ______, resulting in T-lymphocytes being unable to instruct B-lymphocytes to switch their production of immunoglobulins from IgM to IgG, IgA, and IgE.
CD40 ligand
How is hyper-IgM syndrome treated?
- Immunoglobulin replacement therapy
What are the target cells for HIV?
- CD4 T-cells
- Macrophages
What class of virus is HIV?
Exogenous retrovirus (integrated DNA does not remain permanently in the genome)
How does HIV integrate into the host genome?
- RNA is synthesized to cDNA by reverse transcriptase
- Integrase enzyme integrates cDNA into host genome
Where does HIV integrate into the genome?
- At long terminal repeats (LTRs)
People with _____ deficiency are naturally resistant to HIV
CCR5
