Diseases of Immunity Pt 3 Flashcards
Histopath of B cell deficiencies
absent or reduced follicles and germinal centers in lymphoid organs, reduced Ig levels
Infectious consequences of B cell deficiencies
pyogenic bacterial infections, enteric bacterial and viral infections
Histopath of T cell deficiencies
reduced T cell zones in lymphoid organs, reduced DTH reactions to common ags. defective T cell proliferative responses
Infectious consequences of T cell deficiencies
viral and other intracellular microbial infections, some cancers
Histopath of innate immune deficiencies
dependent on which component is defective
Infectious consequences of innate immune deficiencies
pyogenic bacterial and viral infections
Chediak Higashi syndrome
autosomal recessive disorder, failure of phagolysosomal fusion resulting in increased bacterial infections; fatal without a stem cell transplant
Blood smear of Chediak Higashi
giant granules, accumulation of organisms
Presentation of Chediak Higashi pts
defects in melanocytes leading to albinism or grey streaks in hair
Chronic granulomatous disease
GROUP of genetic disorders, failure of superoxide anion production within phagocytes; accumulation of macrophages walls off the infection
Membrane Attack Complex defiiency
C5, 6, 7, 8, 9 can be affected; lysis of cell membrane cannot occur; Neisseria infections are common (meningitis)
Hereditary angioedema
autosomal dominant deficiency of C1 inhibitor
Presentation of hereditary angioedema
headache, dizziness, throat swelling, vomiting, abd pain, bladder and genital swelling, cutaneous edema, cork screw appearance of intestines
Severe Combined Immunodeficiency (SCID)
most common deficiency is in both B and T cell lineages due to a defect in T cell function
X-linked SCID
males, mutation in IL receptors, T cell reduced and B cells unable to make Ab without T cell help
Autosomal Recessive SCID
adenosine deaminase (ADA) deficiency, accumulation of toxic purine metabolites that blocks T cell formation (some B cell influence but lack of Th cells suppresses humoral)
SCID treatments
stem cell transplant, gene therapy
DiGeorge syndrome
primary T cell deficiency due to failure of pharyngeal pouches 3 and 4 (thymus, parathyroids, heart, great vessels)
DiGeorge manifestations
facial and palatal abnormalities, cardiac abn, tetany, immune deficiency (T cell, humoral deficiency)
X-linked agammaglobulinemia
Bruton tyrosine kinase gene defect on x-csome; inability of pre-B cells to mature, presents in early to late childhood
Presentation of agammaglobulenemia
infection by encapsulated bacteria (S. pneumoniae, H. influenzae B, S. pyogenes, S. aureus, P. aeruginosa), viruses, and protozoa (Giardia lamblia)
Hyper-IgM syndrome
encapsulated bacterial infections predominate due to lack of opsonizing antibodies; CD40:CD40L mutations (prevents class switching); High IgM
Hyper-IgM treatment
IVIg, stem cell transplant
Common Variable Immunodeficiency (CVID)
results in hypogammaglobulinemia; most common primary immunodeficiency; encapsulated bacterial infections
CVID presentation
recurrent sinopulmonary infections by pyogenic bacteria due to low IgA, granulomas, chronic diarrhea, autoimmune disease (anemia, thrombocytopenia)
IgA deficiency
familial or acquired, less defense of inhaled and ingested pathogens
Presentation of IgA deficiency
sinus and resp infections, urinary bladder infections, GI infection, autoimmune dz and allergies, anapylactic rxn against RBC transfusion
Transfusion related anaphylaxis
IgA present in transfusion may trigger anaphylactic reaction, red cell washing can prevent reactions
Wiskott Aldrich Syndrome triad
thrombocytopenia, eczema, recurrent infections due to T cell loss and hypogammaglobulinemia
Wiskott Aldrich mutation
WASP gene
Wiskott Aldrich treatment
stem cell transplant
Ataxia Telangiectasia
neurodegenerative disease, vascular malformation, immune deficiency (resp. infections, autoimmune dz, CA); autosomal recessive ATM gene mutation
Examples of secondary immunodeficiency
CA, DM, metabolic dz, chronic illness, treatment-related chemo/rad/immunosupression, AIDS
Acquired Immunodeficiency Syndrome
manifestation when HIV affects body to degree where immune dysfunction results in opportunistic infections, secondary neoplasms, neuro manifestations
Beginnings of AIDS
started in 1980s and was mostly seen in homosexual men, blood transfusion recipients, infants/female; presented as infections ,tumors, neuro impairment
Who is at risk for HIV?
homosexual/bisexual men, IV drug abusers, hemophiliacs, other recipients of blood/blood components, heterosexual contacts, newborns in areas of high female prevalence
Most common modes of HIV transmission
Male->male, Male->female
Parenteral routes of virus transmission
IV drugs, transfusions
Mother to child virus transmission
placental transfer, during delivery with contact of secretions in birth canal, after birth with ingestion of breast milk
HIV virus classification
Retrovirus, lentivirus family
HIV capsid protein
p24
HIV glycoproteins
gp120, gp41
HIV viral enzymes
protease, reverse transcriptase, integrase
HIV LTR gene
initiates transcription, binds TFs
HIV gag gene
encodes for proteins inside the virus (capsid, matrix, nucleocapsid)
HIV env gene
encodes for surface glycoproteins
HIV pol enzymes
encodes for viral enzymes (protease, reverse transcriptase, etc)
Entry of HIV
attaches to CD4 receptor on T cells via gp120, gp41 allows for membrane fusion and inserts viral genome
HIV replication
Reverse transcriptase synthesizes proviral DS DNA from original RNA; integrase inserts proviral DNA into host genome; when host cell activates, LTR is triggered to transcribe viral RNA
Antigenic stimulation of HIV infected cell causes release of what molecule
NF-kB, initiating viral transcription (when it should be upregualating T cell response
HIV release
host cell dies, pyroptosis may occur (inflammasome-mediated)
HIV infection of non-T cells
macrophages, dendritic cells, microglia
B lymphocytes in HIV infection
proliferative response (due to secondary infection)m may become clonal (develop into lymphoma), non-specific hypergammaglobulinemia, impaired humoral immunity
Pathogenesis of HIV
infection of mucosal tissues, death of mucosa memory T cells, infection establishment in lymphoid tissues, spread of infection throughout the body, immune response (triggering partial control of replication), clinical latency
First detectable sign of HIV
viral RNA (use NAT)
Second detectable sign of HIV
p24
Third detectable sign of HIV
antibody to HIV
Window period
time between infection and seroconversion
Acute retroviral syndrome
fever, sore throat, muscle aches, self-limited
Viral set point
end of initial viremic spike, may predict CD4 cell loss and reflects clinical latency
Clinical latency
period of “silent massacre” of CD4 cells, may last years without symptoms
AIDS case definition
AIDS-defining conditions (P. jiroveci pneumonia, chronic cryptosporidiosis, invasive cervical cancer, CD4<200 cell/mm3
HIV treatment course when detected early
HAART initiated, CD4 counts monitored, prophylactic treatment against infections
Manifestations of AIDS
opportunistic infection (Pneumocystis pneumonia, TB, toxoplasma, C. mucositis) and neoplasia (Kaposi Sarcoma and lymphoma)
Pneumocystis jiroveci
opportunistic fungal infection, AIDS defining illness, diffuse or focal radiographically
Kaposi sarcoma
vascular tumor, Human herpesvirus 8, primary effusion lymphoma
AIDS related lymphomas
opportunistic viral infections may lead to EBV lymphoma, decrease in cellular immunity leads to B cell hyperplasia (burkitt lymphoma)
AIDS-defining cancer
cervical and anal cancer–viral driven
Amyloidosis
misfolding of proteins leading to beta-pleated sheets
Types of amyloid
local, systemic, acquired or hereditary, different chemical properties
Where does amyloid tend to manifest?
kidney, brain, heart, liver, fat tissue
Initial presentation of amyloid in kidney
proteinuria and edema
Initial presentation of amyloid in heart
dysrhythmias
Major fibril protein in multiple myeloma (primary amyloidosis)
AL
Major fibril protein in chronic inflammatory conditions
AA
Major fibril protein in familial mediterranean fever
AA
Major fibril protein in familial amyloidotic neuropathies and systemic senile amyloidosis
AATR
Major fibril protein in medullary carcinoma of thyroid
A Cal
