Pathoma Chapter 2B Flashcards
Cytotoxic T cell killing occurs via
Secretion of perforin and granzyme; perforin creates pores that allow granzyme to enter the target cell, activating apoptosis. Expression of FasL, which binds Fas on target cells, activating apoptosis
B Lymphocytes
Immature B cells are produced in the bone marrow and undergo immunoglobulin rearrangements to become naive B cells that express surface IgM and IgD.
B-cell activation occurs via
Antigen binding by surface IgM or IgD; results in maturation to IgM or IgD secreting plasma cells, B-cell antigen presentation to CD4+ helper T cells via MHC class II
What provides the 2nd activation signal
CD40 receptor on B cell binds CD40L on helper T cell
What happens after the 2nd activation of B cells?
Helper T cell then secretes IL-4 and IL-5 (mediate B-cell isotype switching, hypermutation, and maturation to plasma cells)
What is granulomatous inflammation?
Subtype of chronic inflammation, Characterized by granuloma, which is a collection of epithelioid histiocytes
What are epithelioid histiocytes?
macrophages with abundant pink cytoplasm, usually surrounded by giant cells and a rim of lymphocytes
What is granulomatous inflammation divided into?
noncaseating and caseating subtypes
What is noncaseating granulomas?
lack central necrosis
Common etiologies for noncaseating granulomas?
include reaction to foreign material, sarcoidosis, beryllium exposure, Crohn disease, and cat scratch disease,
Caseating granulomas
exhibit central necrosis and are characteristic of tuberculosis and fungal infections
What are the seps involved in granuloma formation?
- Macrophages process and present antigen via MHC class II to CD4+ helper T cells. 2. Interaction leads macrophages to secrete IL-12, inducing CD4+ helper T cells to differentiate into THl subtype. 3. TH1 cells secrete IFN-y, which converts macrophages to epithelioid histiocytes and giant cells.
What is DiGeorge Syndrome?
Developmental failure of the third and fourth pharyngeal pouches
What is DiGeorge Syndrome?
Due to 22qll microdeletion
What does DiGeorge Syndrome presents with?
T-cell deficiency (lack of thymus); hypocalcemia (lack of parathyroids); and abnormalities of heart, great vessels, and face
Severe combined immunodeficiency
defective cell-mediated and humoral immunity
What are the etiologies for SCID?
Cytokine receptor defects, Adenosine deaminase (ADA) deficiency, MHC class II deficiency
Cytokine receptor defects
Cytokine signaling is necessary for proliferation and maturation of B and T cells.
Adenosine deaminase (ADA) deficiency
ADA is necessary to deaminate adenosine and deoxyadenosine for excretion as waste products; buildup of adenosine and deoxyadenosine is toxic to lymphocytes
MHC class II deficiency
MHC class II is necessary for CD4+ helper T cell activation and cytokine production
SCID is characterized by?
susceptibility to fungal, viral, bacterial, and protozoal infections, including opportunistic infections and live vaccines
SCID treatment is?
sterile isolation (‘bubble baby ) and stem cell transplantation.
What is X-Linked agammaglobulinemia?
Complete lack of immunoglobulin due to disordered B-cell maturation, naive B cells cannot mature to plasma cells.
What is X-Linked agammaglobulinemia due to?
mutated Bruton tyrosine kinase; X-linked
How does X-Linked agammaglobulinemia present?
after 6 months of life with recurrent bacterial, enterovirus (e.g., polio and coxsackievirus), and Giardia lamblia infections; maternal antibodies present during the first five months of life are protective.
What is the caveat associated with X-Linked agammaglobulinemia?
Live vaccines (e.g., polio) must be avoided.
What is common variable immunodeficiency?
Low immunoglobulin due to B-cell or helper T-cell defects
CVID increases the risk of what?
increased risk for bacterial, enterovirus, and Giardia lamblia infections, usually in late childhood, Increased risk for autoimmune disease and lymphoma
IgA deficiency
Low serum and mucosal IgA; most common immunoglobulin deficiency
IgA deficiency increases the risk for?
Increased risk for mucosal infection, especially viral; however, most patients are asymptomatic.
Hyper IgM syndrome
Characterized by elevated IgM, Due to mutated CD40L (on helper T cells) or CD40 receptor (on B cells)
What is the effect of the mutation leading to hyper-IgM?
Second signal cannot be delivered to helper T cells during B-cell activation so cytokines necessary for immunoglobulin class switching are not produced
No class switching in hyper IgM syndrome leads to what?
Low IgA, IgG, and IgE result in recurrent pyogenic infections (due to poor opsonization), especially at mucosal sites.
What is Wiscott Aldrich syndrome?
Characterized by thrombocytopenia, eczema, and recurrent infections {defective humoral and cellular immunity)
What is Wiscott Aldrich syndrome due to?
mutation in the WASP gene; X-linked
What are the Complement Deficiencies?
C5-C9 deficiencies, CI inhibitor deficiency
C5-C9 deficiencies
increased risk for Neisseria infection (Ngonorrhoeae and N meningitidis)
CI inhibitor deficiency
results in hereditary angioedema, which is characterized by edema of the skin (especially periorbital, Fig. 2.3) and mucosal surfaces
Autoimmune disorders are characterized by?
immune-mediated damage of tissues, 1% prevalence in the US, Involves loss of self-tolerance
In autoimmune disorders what does loss of self tolerance involve
Self-reactive lymphocytes are regularly generated but undergo apoptosis (negative selection) in the thymus (T cells) or bone marrow (B cells) or become anergic (due to recognition of antigen in peripheral lymphoid tissues with no 2nd signal).
Autoimmune disease is more common in?
women; classically affects women of childbearing age
What is the etiology for autoimmune disease?
It is likely an environmental trigger in genetically susceptible individuals (increased incidence in twins and associated with certain HLA subtypes).
What is systemic Lupus Erythematosus?
Systemic autoimmune disease, antibodies against tbe host damage multiple tissues via type II (cytotoxic) and type III (antigen-antibody complex) hypersensitivity.
Systemic Lupus Erythematosus is more common in?
women, especially African American females
Clinical features of systemic Lupus Erythematosus include?
Fever and weight loss, Malar ‘butterfly’ rash, especially upon exposure to sunlight, Arthritis, Pleuritis and pericarditis (involvement of serosal surfaces), CNS psychosis, Renal damage, Endocarditis, myocarditis, or pericarditis (can affect any layer of the heart), Anemia, thrombocytopenia, or leukopenia (due to autoantibodies against cell surface proteins), Renal failure and infection are common causes of death.
Anemia, thrombocytopenia, or leukopenia in SLE is due to?
autoantibodies against cell surface proteins
Most common causes of death in SLE?
Renal failure and infection
What is a classic finding for systemic lupus eythematosus?
Libman-Sacks endocarditis is and is characterized by small, sterile deposits on both sides of the mitral valve.
What is the most common clinical features of systemic Lupus Erythematosus?
Diffuse proliferative glomerulonephritis, though other patterns of injury also occur.
Systemic Lupus Erythematosus and anemia, thrombocytopenia, or leukopenia is due to?
autoantibodies against cell surface proteins
What are common causes of death for SLE?
renal failure and infection
