Immunology Flashcards
HLA- A, B, C are encoded by MHC Class __. HLA-DR, DP, AD are encoded by MHC Class ___.
I, II
remember 1 letter = MHC class I, 2 letters = Class II
MHC Class I mediates _____ immunity while MHC Class II mediates ______ immunity.
MHC Class I = CD8+ = viral immunity
(intracellular pathogens)
MHC Class II = CD4+ = bacterial immunity (extracellular pathogens)
Note: there are a few exceptions. For example when a bacteria is intracellular (e.g. listeria), MHC Class I will be used.
MHC II only found on ______ cells.
Antigen presenting cells
macrophage, dendritic cell, B cells
What is the mnemonic for remembering which autoimmune diseases are associated with HLA-B27?
“PAIR”
Psoriasis
Ankylosing spondylitis
IBD
Reiter’s syndrome
HLA-A3 = ________
Hereditary hemochromatosis
HLA-B8 = _______ Disease.
Grave’s
HLA-DR2 = What 4 diseases?
MS, Hay fever, SLE, Goodpasture’s
DM Type I = HLA-_ and HLA- _
DR3 and DR4
RA = HLA-__
DR4
What 2 diseases are associated with HLA-DR5?
Pernicious anemia
Hashimoto’s
HLA-DR7 = _____ syndrome
Steroid-responsive nephrotic syndrome
What are the cytokines which enhance NK cell activity (aka killing of virally-infected and tumor cells)?
IL-12
IFN-beta
IFN-alpha
When a dendritic cell picks up a viral pathogen it makes _______ cytokines to stimulate a CD__+ T cell aka _____.
Virus -> IFN-alpha, IFN-beta -> CD8+ T cell, aka cytotoxic T lymphocyte
When a dendritic cell picks up an intracellular bacterial pathogen it makes _______ cytokines to stimulate a CD__+ T cell aka _____.
Intracellular bacteria -> IFN-gamma, TNF-alpha, IL-2 -> CD4+ TH1 helper T cells
When a dendritic cell picks up a parasitic pathogen it makes _______ cytokines to stimulate a CD__+ T cell aka _____.
Parasite -> IL-4, IL-5, IL-13 -> CD4+ TH2 cells which go on to activate B cells to kill the worm
When a dendritic cell picks up a extracellular bacteria and fungus pathogen it makes _______ cytokines to stimulate a CD__+ T cell aka _____.
Extracellular bacteria or fungus -> IL-6, IL-17 -> CD4+ TH17 cells which go on to activate B cells to make antibodies against and recruit neutrophils
What does IL-8 do?
Neutrophil chemotaxis and phagocytosis upon arrival
The “acute” allergic response is anything that happens within _______.
Minutes to hours
Due to pre-formed IgG Abs (Type II hypersensitivity)
What is Chronic Granulomatous Disease? What test is a tip off?
X-linked mutation affecting NADPH oxidase which is normally activated within phagocytes to produce ROS AND to activate granule proteases (e.g. elastase, cathepsin G) within phagosomes.
Dysfunction of NADPH oxidase leads to impaired intracellular killing by neutrophils and macrophages leading to recurrent bacterial and fungal infections.
Failure of neutrophils to turn blue upon nitroblue tetrazolium testing indicates CGD.
How does being catalase positive help bacteria evade neutrophil destruction?
Catalase destroys hydrogen peroxide that bacteria generate themselves
Recurrent viral, fungal, sinopulmonary, and opportunistic infections (e.g. PJP) is indicative of _____.
SCID, or some other immunocompromised state
What is the pathogenesis of sarcoidosis?
Sarcoidosis is thought to result from a dysregulated cell-mediated immune response lead by Th1 CD4+ T cells which secrete IL-2 and IFN-gamma. This activates macrophages, promoting non-caseating granuloma formation.
Sarcoidosis is most common in what patient population?
African Americans
Especially women 20-39 years old
What are the 2 most common forms of SCID?
Most common = X-linked recessive
Second most = adenosine deaminase deficiency (build up of adenosine is cytotoxic to B and T cells).
How do superantigens (e.g. TSS toxin from s. aureus) work to cause hemodynamic collapse?
Superantigens cause widespread activation of helper T cells and antigen presenting cells (mainly macrophages) causing widespread T cell activation.
T cells secrete IL-2 cytokines and macrophages secrete IL-1 and TNF causing capillary leakage, hypotension, vascular collapse, skin findings, shock, and multiorgan failure.
What is the most common systemic vasculitis in children? How is it characterized?
Henoch-Schonlein purpura (HSP).
Characterized by circulating IgA-antigen immune complexes (Type III hypersensitivity) that deposit in the walls of small vessels and renal mesangium.
Presents as palpable purpura, arthralgias, abdominal pain, possible hematuria.
Tx is generally supportive as it is self-limited unless an intussusception occurs as a result of the GI problems.
Antigens are presented on MHC Class I _____ chains and _____.
Heavy chain
Beta 2 microglobulin
How do cytotoxic T cells actually kill?
Perforin and granzymes OR
IFN alpha and IFN beta bind to receptors on infected + neighboring cells causing transcription of antiviral enzymes that are capable of halting protein synthesis in the infected cell.
Examples = RNase L and protein kinase E.
One cool thing is that this process only works in the presence of double-stranded RNA (i.e. cells with viral genome present) so the uninfected neighboring cells are able to continue as usual.
Albinism, neurologic defects, nystagmus, immunodeficiency = ?
Chediak-Higashi
Autosomal recessive
Characterized by a defect in neutrophil phagosome lysosome fusion causing giant lysosomal inclusions visible on LM and peripheral smear.
Tryptase = \_\_\_\_\_ cells Myeloperoxidase = \_\_\_\_\_
Tryptase = mast cells Myeloperoxidase = neutrophils
What is the co-stimulatory signal expressed on Th cells for activation?
CD40L. They bind to CD40 on B cells to activate them.
Th1 cells regulate a cell-mediated response via
IL-2 and IFN-gamma
Th2 cells regulate a humoral-mediated response via
IL-4, IL-5
Th1 and Th2 tend to inhibit each other to make a specific immune response via:
Th1 makes IL-10
Th2 makes IFN gamma
The ___ chain has VDJ recombination and the ___ chain has VJ combination
heavy = VDJ light = VJ
The alternative complement pathway is always ___.
on
It is mediated by C3 and held in check by “DAF” on host cells
Ig_ and Ig_ are the best at activating complement via the classical complement cascade.
IgG and IgM
Deficiency of C5-C8 leads to _______ bacteremia.
Neisseria
What is a helpful mnemonic for remembering cytokines?
“Hot T-Bone stEAk”
IL-1: fever (hot) IL-2: T cells IL-3: Bone marrow IL-4: IgE IL-5: IgA
“clean up on aisle 8” -> neutrophils recruited by IL-8 to clear infections
Which cytokines are involved in the adaptive immune system?
IL-2
IL-4
IL-5
IL-10
IL-12
2x2=4
5x2=10
12
What are the interleukins that induce fever?
IL-1
IL-6
TNF-alpha
IL-6 also induces liver production of acute phase reactants
Asthma is a Type __ Hypersensitivity
I
C__ and C__ act as chemoattractants for neutrophils and phagocytes.
C3a and C5a
Serum sickness is a Type ___ hypersensitivity. IgG and IgM complexes deposit and can cause localized ______ consumption, ultimately leading to hypo______.
III
Complement
Hypocomplementemia (decreased serum C3)
In general, Type ___ hypersensitivities tend to be limited to an organ while Type ___ involve vessels and are more systemic.
Name examples.
II = limited III = systemic
Type II: Hemolytic Anemia Pernicious anemia Rheumatic fever Goodpasture's Grave's Bullous pemphigoid Pemphigus vulgaris Myasthenia Gravis
Type III: SLE RA PAN PSGN Serum sickness Arthus rxn Hypersensitvity pneumonitis (farmer's lung)
_____ syndrome aka thymic aplasia
DiGeorge
Absence of thymic shadow
-> decreased T cells
Lymphocytes enter the lymph node via the ___ and the spleen via the _____.
Lymph node = HEV
Spleen = central arteriole
In the spleen the PALS around the central arteriole is the ___ cell zone
T cell
The marginal zone in the spleen contains _______.
Macrophages (antigen presenting cells)
Cyclosporine and tacrolimus are _____ inhibitors which _______.
Calcineurin inhibitors
Block T cell signaling
A bronchoalveolar lavage in sarcoidosis will show an elevated CD_:CD_ ratio which sequesters them so they don’t actually respond to other T cell mediated antigens.
CD4 > CD8
Three distinguishing features of sarcoidosis from other granulomatous diseases is the presence of:
Hypercalcemia (via overactivated 1alpha hydroxylase)
Erythema nodosum on the shins
Anterior uveitis
What are patients working in “nuclear and aircraft/aerospace industries” likely to get?
Berylliosis from inhaling beryllium dust. Causes a sarcoid-like interstitial lung disease.
Which interleukin is responsible for initiating isotype switching?
IL-4
Remember TH2 cells activate the humoral immune system via IL-4 and IL-5 secretion
Granulomas are formed by what 2 cell types?
CD4+ T cells
++++macrophages
A blood transfusion in an ABO matched donor can still cause an immediate transfusion reaction if the patient has what deficiency:
IgA
and the transfused RBCs will contain IgA
Rheumatoid Factor (RF) is an antibody (typically IgM) specific for the ________.
Fc component of IgG
RF binds circulating IgG and ACPAs (anti-citrullinated protein antibodies) bind modified self-proteins forming immune complexes that deposit on the synovium and cartilage -> complexes activate complement contributing to chronic inflammation and joint destruction.
Positive C-ANCA = ?
CREST syndrome (scleroderma) Wegener's Granulomatosis
Positive Anti-dsDNA = ?
What else would be positive in these patients?
SLE
+ antiphospholipid antibody (although this can be a stand alone disease)
Reactive arthritis = can’t pee, can’t see, can’t climb a tree. What are the more specific symptoms of above mnemonic?
Asymmetric oligoarthritis, can be dactylitis or sacroilitis
Conjunctivitis
Urethritis
Hyperkeratotic vesicles of palms and soles
What are common infections preceding reactive arthritis?
GU: Chlamydia trachomatis
Enteritis: Salmonella, Shigella, Yersinia, Campylobacter, C. diff
Although T-cell deficiency would lead to superficial candidiasis (and other fungal infections), disseminated aka hematogenous spread of candida is often due to ________penia.
Neutropenia
or otherwise immunocompromised such as receiving chemo
What is the cell surface marker for macrophages?
CD14
Many tumor cells evade the immune system by expressing ______ which downregulates the immune response by inhibiting cytotoxic T cells.
PD-1
This is why new monoclonal Abs for tumor suppression bind to PD-1 and block its action.
B7 + CD28 = T cell _______
B7 + CTLA4 = T cell ______
Activation
Suppression
What histopathology is seen in the acute phase of transplant rejection?
Dense infiltrate of mononuclear cells (mostly T lymphocytes).
The rejection occurs due to host T-lymphocyte sensitization against graft (foreign) MHC antigens.
What immunodeficiency leads to recurrent neisseria infections?
Failure of Membrane Attack Complex (MAC) to form (i.e. C5b-C9 of complement cascade).
What is ABO disease? When can it occur?
Attack of an A or B fetus in an O negative mother. These mothers will have Anti-A and Anti-B antibodies from mimicking antigens in food, bacteria, or other viruses. These are IgGs and can thus cross the placenta and cause hemolysis in the fetus.
Note these antibodies are pre-existing and thus can attack the fetus of a first pregnancy (unlike Rh disease).
When Anti-A and Anti-B are naturally occurring, they are type IgM which cannot cross the placenta.
Anti-toposiomerase I (Scl-70) = ?
Scleroderma/CREST
Positive C-ANCA = ?
Scleroderma/CREST
Anti-U1 RNP = ?
CAN be SLE but most likely mixed connective tissue disorder
Anti-Jo-1 = ?
Polymyositis or dermatomyositis
Polymyositis = _____misial inflammatory infiltrate while dermatomyositis = ______misial.
Poly = endo (within muscle fascicle) Dermato = peri
C-ANCA aka ______
Located in the _______
+ in
C-ANCA = PR3
Located in the cytoplasm (C)
+ in Wegener’s granulomatosis and CREST
P-ANCA aka ______
Located in the _______
+ in _________
P-ANCA = MPO
Located in the perinuclear lysosomes
+ in everything else except Wegener’s
What is the triad of presenting symptoms of Wegener’s Granulomatosis (aka GPA)?
Nose - sinus and septal problems, saddle nose deformity
Lung - Recurrent pneumonitis, interstitial lung disease, alveolar hemorrhage
Kidneys - glomerulonephritis
Microscopic polyangiitis MOSTLY affects the ______ but can also affect the ______.
Mostly lungs
Some kidney
What is the important distinguishing feature of Churg-Strauss?
Eosinophilia
often a history of asthma
Cryoglobulinemia is a Type ___ hypersensitivity and is cahracterized by:
Type III
Antibody immune complexes. One of the most common is IgM clumps, but it can be any Ig.
Cryoglobulinemia is associated with Hepatitis ___ and is most often seen in:
Hep C
Older women
Although Goodpasture’s disease is primarily characterized by linear staining of the basement membrane by Abs, these Abs also upregulate _______ leading to _______.
Abs induce complement -> complexes form in the kidneys causing crescentic glomerulonephritis
CD3 is found on all mature ___ cells.
T
X-linked SCID patients are deficient in IL-___ which is needed for preservation of immature B and T cells.
IL-7
What is the role of the ATM gene in Ataxia-Telangiectasia?
Surveillance of DNA damage and stalling the cell cycle to give time for repair -> deficiency = deficient B and T cells
What lab findings will you see in Ataxia-Telangiectasia?
Especially low serum IgA (why they get so many sinopulmonary infections)
Elevated serum alfa-fetoprotein (AFP)
