Immunology Uworld

* autoantibodies that are useful in the diagnosis of SLE include:

* Interleukin-2 (IL-2) is produced primarily by helper T cells and is the major growth factor for T
lymphocytes. Antigen binding to the T cell receptor stimulates the secretion of IL-2 and the
expression of IL-2 receptors (IL-2R). The IL-2/IL-2R (autocrine) interaction then stimulates the
growth, differentiation, and survival of antigen-specific CD4+ T cells and CD8+ T cells. IL-2
also promotes the growth of B cells and activates natural killer (NK) cells and monocytes.

* bacteria and fungi responsible for infections in CGD are catalase-positive organisms that can
destroy their own hydrogen peroxide. The most common organisms are Staphylococcus
aureus, Burkholderia cepacia, Serratia marcescens, Nocardia, and Aspergillus.
* TSST acts as a superantigen that activates large numbers of helper T cells (compared to a
regular antigen, which activates few helper T cells). Superantigens interact with major
histocompatibility complex molecules on antigen-presenting cells (eg, macrophages) and with
the variable region of the T lymphocyte receptor to cause a nonspecific, widespread activation
of T lymphocytes. Activation of T cells is responsible for the release of interleukin (IL)-2 from
the T cells and IL-1 and tumor necrosis factor from macrophages. These ILs cause capillary
leakage, circulatory collapse, hypotension, shock, fever, skin findings, and multiorgan failure
* Reactive lymphocytes are activated, pathogen-specific cytotoxic T cells and natural killer
cells that form in response to certain intracellular infections (eg, HIV, cytomegalovirus,
toxoplasmosis); they are particularly linked to infectious mononucleosis, a primary Epstein-Barr
virus characterized by fever, pharyngitis, adenopathy, splenomegaly, and se
vere fatigue
* Reactive lymphocytes are effector cells that contain cytotoxic granules composed of perforin
(creates holes in the infected cell's membrane) and granzymes (enter the cytoplasm of
infected cells and trigger cell death), which are released in response to foreign antigens on the
surface (MHC class I receptors) of infected host cells.
*
* Tolerance is immunologic unresponsiveness to self antigens. Central tolerance is acquired
within the fetal thymus during negative selection. Peripheral tolerance develops by means of
T-cell anergy, which is the functional inactivation of T-cells that are reactive to self
antigens.Isotype switching (from IgM to other types of immunoglobulins) also occurs in the
germinal centers late in the primary response, providing activated B-cells the ability to produce
antigen-specific antibodies of differing isotypes. Heavy chain constant regions are isotype-
specific and distinguish the 5 isotypes (IgM, IgG, IgA, IgE, and IgD), while the variable regions
are antigen-specific.Light chains are antigen-specific and do not determine isotype.
* Isotype switching first requires interaction of the CD40 receptor on activated B-cells with the
CD40 ligand (CD154) expressed by activated T-cells. Afterward, isotype switching can occur
through genetic rearrangement of the heavy chain constant regions. This process is
modulated by T-cell cytokines such as IL-2, IL-4, IL-5, IL-6, and IFN-γ. After the primary
immune response, subsequent encounters with the same antigen generate a predominantly
IgG response (or IgA in the case of a mucosal response).Reactive lymphocytes are effector
cells that contain cytotoxic granules composed of perforin (creates holes in the infected cell's
membrane) and granzymes (enter the cytoplasm of infected cells and trigger cell death), which
are released in response to foreign antigens on the surface (MHC class I receptors) of infected
host cells.
* In MM, neoplastic plasma cells crowd the bone marrow, leading to impairments in normal
hematopoiesis. B-cell development is particularly affected, which reduces plasma cell
diversity and limits the generation of targeted immunoglobulins against infectious agents.
Therefore, patients with MM have increased risk of recurrent bacterial infections, particularly of
the urinary tract, lungs, and sinuses. Although patients with MM have high levels of circulating
monoclonal immunoglobulin, monoclonal immunoglobulin does not provide immunity against a
diverse range of pathogens. MM is also associated with normocytic anemia (due to ineffective
erythropoiesis), bone pain (due to osteolytic lesions), hypercalcemia, and renal insufficiency
(due to clogging of the tubules with immunoglobulin light chains).
*

*
* virally infected “respiratory epithelial cells” would secrete interferons α and β, not interferon
γ.
* Type I interferons (α and β) are synthesized by most human cells in response to viral
infections. Once secreted, α and β interferons bind to type I interferon receptors found on
infected and neighboring cells (autocrine/paracrine signaling). This results in transcription of
antiviral enzymes capable of halting protein synthesis, such as RNase L (endonuclease that
degrades all RNA in the cell) and protein kinase R (inactivates eIF-2, inhibiting translation
initiation). However, these enzymes become active only in the presence of double-stranded
RNA, which forms in infected cells as a result of viral replication. As a result, normal
metabolism and protein synthesis can continue in uninfected cells but is selectively inhibited in
virally infected cells
* Ubiquitin functions as a tag that is attached to proteins to mark them for destruction. This
process is performed by ubiquitin ligases, enzymes that recognize specific protein substrates
and catalyze ubiquitin attachment. These tagged proteins are then taken up by the
proteasome, where they are broken down into their constituent oligopeptides and, eventually,
amino acids.
* Interferon gamma (IFN-gamma), a pleiotropic TH1 cytokine, is a key factor in the elimination
of these infections. Specifically, macrophages infected with mycobacteria produce interleukin
12, which in turn stimulates T cells and natural killer cells to produce IFN-gamma. IFN-gamma
then binds to its receptor, leading to receptor dimerization and activation of Janus kinases 1
and 2. This results in nuclear signaling via STAT1 and transcription of IFN-gamma-regulated
genes, which promote mycobacterial killing by phagocytes. IFN-gamma also enhances viral
and parasitic resistance by increasing expression of MHC and intrinsic defense factors.
* The tuberculin skin test (TST) is a common screening test for M tuberculosis exposure. It
involves injection of tuberculin antigens under the skin, which provokes a T-cell-mediated,
delayed-type hypersensitivity reaction in those who have been previously exposed (induration
at 48-72 hours). Because the cell-mediated response to M tuberculosis takes several weeks
to form, recently exposed patients often have negative initial TST testing. Conversion usually
occurs within 8 weeks.
* Most patients with primary tuberculosis have no symptoms and no chest x-ray findings;
however, after several months, a Ranke complex (calcified lower lobe nodule and ipsilateral
hilar lymph node) can often be seen on x-ray.
* Dendritic cells are avid antigen presenting cells that constantly sample their environment by
endocytosis and become activated upon encountering a foreign antigen. When activated,
dendritic cells migrate to the lymph nodes and spleen where they display antigen with MHC II
and co-stimulatory molecules to activate T-cells and B-cells.
* Natural killer (NK) cells are responsible for the destruction of cells with decreased or absent
MHC class I proteins on their surfaces. Such changes in MHC I antigen expression occur in
virus-infected cells and tumor cells.
* 5-Hydroxyicosatetraenoic acid (5-HETE) is produced by a variety of immune cells and serves
as a leukotriene and lipoxin precursor. It also causes neutrophil and macrophage chemotaxis
and neutrophil degranulation.
Importance of hepatitis B serological markers
HBsAg
* HBV surface glycoproteins
* Detectable during acute infection
* Persistence >6 months = chronic infection
HBeAg
* HBV polypeptide
* Detectable during acute infection
* Indicates ↑ viral replication & infectivity
Anti-HBc IgM
* First sign of acute infection
* Present during window phase prior to HBsAg & HBeAg
Anti-HBs
* Seen with cleared infection or vaccination
* Confers long-term immunity
Anti-HBe
* Develops in cleared infection & later in chronic infection
* Indicates ↓ viral replication & infectivity
Anti-HBc IgG
* Present in both acute & chronic infection
* Not present after vaccination
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* Pro-T cells arrive at the thymus as "double negative" cells – indicating that they lack both
CD4 and CD8 antigens and begin their differentiation in the subcapsular zone. Next, the
process of TCR beta gene rearrangement occurs with simultaneous expression of both CD4
and CD8. Once in thymic cortex, the alpha genes rearrange to produce a functional alpha-beta
TCR. Subsequently, the processes of positive and negative selection occur with cells that fail
either of these tests being eliminated by apoptosis.
* Negative selection occurs after positive selection and is the process by which T cells
possessing TCRs that bind with high affinity to self antigen or self MHC class I or II are
eliminated by apoptosis. Negative selection occurs in the thymic medulla and involves
interaction of the developing T cells with thymic medullary epithelial and dendritic cells. This
process serves to eliminate T cells that may be overly autoreactive against self antigens and
therefore may play a role in autoimmunity if not destroyed. This results in a population of T
cells that have only an appropriately low affinity for self MHC molecules.
* Affinity maturation is the process of enhancing the hypervariable region antigen binding
affinity that occurs after initial binding of antigen to membrane-bound immunoglobulin on a
naïve B lymphocyte and subsequent migration of that B-lymphocyte to a lymph node. Within
the germinal center of the lymph node, affinity maturation is accomplished by the process of
somatic hypermutation where the DNA coding for the immunoglobulin variable region is
mutated randomly at a very high rate. This process results in new immunoglobulins with
similar, better, or worse affinity for the antigen; only B cells expressing antibody with enhanced
affinity for antigen will be selected for. This process does not occur in T-lymphocyte
maturation.
* Contact dermatitis is a type IV (delayed-type) hypersensitivity reaction that occurs in 2
distinct phases:
* The sensitization phase leads to the creation of hapten-specific T cells and takes 10-14 days.
Cutaneous dendritic cells take up the haptens and express them on MHC-I and MHC-II
molecules as hapten-conjugated peptides. These dendritic cells travel to the draining lymph
nodes and interact with hapten-sensitive CD4+ and CD8+ T cells, causing activation and
clonal expansion.
* The elicitation phase occurs within 2-3 days following re-exposure to the same antigen (or
following sensitization after first exposure to a highly antigenic antigen such as urushiol). In
this phase, the hapten is taken up by skin cells and causes activation of hapten-sensitized T
cells in the dermis and epidermis. This results in an inflammatory response and the clinical
manifestations of contact dermatitis.
* acute serum sickness, a condition caused by tissue deposition of circulating immune
complexes (type III hypersensitivity). The most common manifestations include fever, pruritic
skin rash, and arthralgias that begin 7-14 days after exposure to an antigen.
Lymphadenopathy and proteinuria may also occur in some patients. Histologic examination of
affected tissues typically shows small vessel vasculitis with fibrinoid necrosis and intense
neutrophil infiltration.
*Leukotriene C4 and its relatives, leukotriene D4 and E4, cause vasoconstriction, increased
vascular permeability, mucous hypersecretion, and bronchospasm.
*Proliferating Th1 cells migrate to sites of infection where they release interferon-gamma, a
crucial cytokine that activates macrophages. This improves their ability to kill ingested
mycobacteria and allows them to produce TNF-α, a proinflammatory cytokine that helps
recruit additional monocytes and macrophages. Activated macrophages can also differentiate
into epithelioid and Langhans giant cells that surround residual foci of mycobacteria, walling
them inside a necrotic, "cheese-like" area of caseation. For most individuals, this
granulomatous response successfully limits the bacteria from spreading and effectively
controls the infection.
*Granulomas often form after tissue macrophages encounter pathogens or substances that
cannot be easily digested or removed. M tuberculosis is able to evade intracellular killing by
macrophages and survive and reproduce within phagolysosomes. Infected macrophages
travel to the draining pulmonary lymph nodes where they present mycobacterial antigens to
naïve CD4 helper T cells. They also secrete interleukin-12, which induces activated T helper
cells to differentiate into T helper subtype 1 (Th1) cells.
*Lysozyme is an antimicrobial enzyme found in specific granules of neutrophils and bodily
secretions (tears, mucus). Lysozyme functions by hydrolyzing bonds within the peptidoglycan
cell walls of bacterial organisms. It is an important component of innate immunity, not
hypersensitivity reactions
*Contact dermatitis, granulomatous inflammation, and reactive skin testing (eg, tuberculin skin
test, Candida extract skin reaction) are all examples of type IV (T Cell–mediated) delayed-
type hypersensitivity reactions. When reexposed to an antigen, previously sensitized T
lymphocytes proliferate and release inflammatory cytokines that promote cell-mediated
cytotoxicity (CD8+ T cells) and/or macrophage recruitment and activation. The resulting tissue
damage and swelling is typically evident 24-48 hours after exposure
*Class II MHC peptides are displayed only by antigen presenting cells. MHC Class II is used to
present antigens that antigen presenting cells (dendritic cells, macrophages and B-
lymphocytes) have encountered in the body and have taken up by phagocytosis or endocytosis
*Endotoxin in the cell membrane of gram-negative bacteria can cause rapid-onset fever and
hypotension due to activation of toll-like receptors on cells of the innate immune system.
*Acute cessation of blood flow through an organ immediately after anastomosis of recipient
vessels to donor vessels is characteristic of hyperacute rejection. It occurs due to preformed
antibodies in the recipient that are directed against donor antigens.
*During infection, macrophages and surrounding endothelial cells release cytokines such as
interleukin-8 (IL-8) that trigger neutrophils to enter the site of infection via chemotaxis. IL-8
also induces phagocytosis in neutrophils once they have arrived.
*Bcl-2 is an apoptosis inhibitor. When Bcl-2 is overexpressed, cell death is delayed and an
accumulation of indolent malignant cells occurs. Bcl-2 involvement has been implicated in
follicular cell lymphomas
*The candidal antigen skin test is used to determine the presence of cellular, or T cell-
mediated, immunity through the detection of a delayed-type hypersensitivity reaction (type
IV). The key cells involved are macrophages, CD4+ helper T cells, and CD8+ cytotoxic T
cells. Macrophages present the injected candida antigen to CD4+ helper T cells. In response,
CD4+ T cells secrete cytokines that recruit CD8+ T cells to the area and produce the
characteristic signs of induration and erythema. CD4+ and CD8+ T cells both produce
interferon gamma, which stimulates phagocytosis of Candida by the macrophages. Failure to
generate a response is referred to as anergy, which is expected in SCID patients who are
deficient in both T and B cell lines. Virtually all people are sensitized to Candida, and so the
candidal skin test can be used as a positive control for other antigens (eg, tuberculin skin
testing).
*Because IgM circulates in pentameric form (five IgM molecules joined together at their Fc
regions by a J chain peptide), it is much more effective in initiating the complement cascade
than IgG which circulates in monomeric form (a single circulating immunoglobulin as pictured
above). The complement binding site on both IgG and IgM is located in the Fc portion closer to
the hinge region
*23-valent pneumococcal polysaccharide vaccine (PPSV23, Pneumovax) protects against a
wider range of serotypes (Choice E), but antibody levels decline over approximately 5 years.
In addition, PPSV23 is not immunogenic in children age <2 due to their relatively immature
humoral antibody response. Therefore, PPSV23 is recommended for all adults age >65 and for
those age 2-64 with certain medical conditions (eg, diabetes, chronic pulmonary or
cardiovascular disease).
*13-valent pneumococcal conjugate vaccine (PCV13, Prevnar) contains a nontoxic diphtheria
protein conjugated to the polysaccharides that boosts the immune response through T cell
recruitment. This conjugation allows for development of memory B cells, higher and longer-
lasting antibody levels, and less mucosal carriage (herd immunity). Therefore, PCV13 is
strongly immunogenic in infancy and part of routine childhood vaccinations. Similar to
PPSV23, PCV13 is recommended for immunocompromised patients and adults age >65.
*Eosinophil proliferation and activation during parasitic infection is stimulated by IL-5
produced by TH2 and mast cells. When a parasite invades the mucosa or enters the
bloodstream, it is coated by IgG and IgE antibodies that bind the Fc receptors located on the
eosinophil cell surface. This triggers eosinophil degranulation and release of cytotoxic proteins
(eg, major basic protein) and reactive oxygen intermediates, substances that damage and
destroy antibody-bound parasites. This mechanism is an example of antibody-dependent
cell-mediated cytotoxicity (ADCC), which is also used by macrophages, neutrophils, and
natural killer cells.
*In agammaglobulinemia, germinal centers and primary lymphoid follicles do not form due to
an absence of B cells
*leads to compromised cell-mediated and humoral immunity with the eventual development of
severe viral and bacterial infections as maternal immunity wanes. Other common features
include mucocutaneous candidiasis, persistent diarrhea, and failure to thrive.
*When transfused with blood products (eg, red blood cells, platelets, fresh frozen plasma)
containing small amounts of IgA, these patients can develop potentially fatal anaphylaxis.
Therefore, patients with severe IgA deficiency should wear medical alert bracelets and receive
blood products that are washed of residual plasma or from an IgA-deficient donor.
*Some intracellular bacterial pathogens (eg, Listeria, Rickettsia) have virulence factors that
allow them to escape the phagosome and replicate within the cytosol. These pathogens are
primarily processed by the proteasome (rather than the lysosome), leading to the display of
bacterial protein fragments on MHC class I molecules. MHC class I molecules stimulate
cytotoxic T cells (CD8 lymphocytes). In contrast, phagocytosed bacteria that remain within
the phagosome (eg, M tuberculosis) are broken down by the lysosome and displayed on MHC
class II molecules, which activate CD4, not CD8, cells.
*The center of the granuloma is acidic and hypoxic, which causes it to appear acellular,
necrotic, and "cheese-like" (caseating). Granulomas typically limit mycobacterial proliferation
but do not fully eliminate the infection.
*Under the influence of inflammatory stimuli, cell membrane phospholipids release arachidonic
acid, a precursor to the eicosanoid inflammatory mediators (eg, prostanoids, leukotrienes,
lipoxins). The most potent chemotactic eicosanoid is leukotriene B4. In contrast, the
cysteinyl-containing leukotrienes (eg, LTC4, LTD4, LTE4) cause bronchospasm and increase
bronchial mucus secretion and are important in asthma pathogenesis
*HBV is considered a stealth virus because it possesses virulence factors that block portions
of the innate immune system, including the release of interferon-gamma from infected cells.
However, HBV immunization does not significantly affect the innate immune system.
*HBsAg is a collection of envelope glycoproteins found on the surface of HBV; these
glycoproteins mediate attachment of the virus to hepatocytes and subsequent viral entry.
Patients who adequately respond to the HBV vaccine generate anti-HBs antibodies, which
bind to circulating viral particles and prevent attachment to and penetration of hepatocytes.
*class switching occurs by splicing out DNA coding for different types of the heavy chain
constant region until the desired isotype is reached. The variable region, and therefore the
antigenic specificity of the antibody, stays the same
*Protein kinase A is a component of the cAMP-associated signaling system. The binding of a
ligand to a G-protein-linked receptor results in adenylyl cyclase activation and the release of
cAMP. Elevated levels of cAMP activate protein kinase A.
*Intrinsic apoptosis is mediated by a group of bcl-2 proteins. Some of the components of this
system are pro-apoptotic (eg, Bak, Bax, and Bim proteins), while others are anti-apoptotic (eg,
Bcl-x and Bcl-2 proteins). Apoptotic signals tip the balance between these two forces,
resulting in changes of the inner mitochondrial membrane. These changes are responsible for
the formation of the mitochondrial permeability transition (MPT) and the release of cytochrome
c and other pro-apoptotic proteins into the cytoplasm, which then activate caspases. In
extrinsic apoptosis, the binding of the death ligand and the death receptor allows for pro-
caspase molecules to be brought into close proximity.
*Caspases are proteolytic enzymes that destroy cell components. They contain cysteine and
are able to cleave aspartic acid residues (cysteine-aspartic-acid-proteases). The eleven
caspases that have been identified are classified as either initiator or effector caspases.
Initiator caspases activate the effector caspases, which then cleave the cellular proteins.
*Cells damaged by ultraviolet light, heat, hypoxia, toxins, or radiation display intrinsic apoptotic
signals (eg, phosphatidylserine or thrombospondin) on their plasma membranes. Extrinsic
apoptosis, in contrast, is induced by the tumor necrosis factor (TNF) when bound to tumor
necrosis factor receptor 1 (TNFR1) or the Fas ligand when bound to cell surface receptor Fas.
*The Monospot test assesses the serum's ability to agglutinate sheep erythrocytes. It is
positive in the presence of heterophile antibodies and is used to diagnose infectious
mononucleosis due to Epstein-Barr virus.
*Anticentromere antibodies are found in the majority of patients with CREST syndrome.
*Antibodies to double-stranded DNA (anti-dsDNA) are specific for systemic lupus
erythematosus.
*Rheumatoid factor is an antibody (typically IgM) specific for the Fc component of IgG.
Rheumatoid factor binds circulating IgG and ACPAs bind modified self-proteins, forming
immune complexes that deposit on the synovium and cartilage. These complexes activate
complement in those locations, contributing to chronic inflammation and joint destruction
*B lymphocytes undergo affinity maturation, cells that exhibit a stronger affinity for the antigen
(which acts as a limited growth resource) are able to proliferate more than cells with lower
affinity. This results in cells that are more efficient and accurate in binding to pathogens.
Affinity maturation does not involve the Fas pathway.
*Upon binding Fas ligand (FasL), the receptors trimerize, allowing their death domains to form
a binding site for an adapter protein called Fas-associated death domain (FADD). Receptor-
bound FADD then stimulates the activation of initiator caspases (8 & 10) that begin an
activation cascade culminating in the activation of executioner caspases (3 & 6). These initiate
the terminal processes of apoptosis, including cleavage of DNA, fragmentation of the nucleus,
organelle autodigestion, and plasma membrane blebbing.
*
TH1 TH2
Type of immunity Cell-mediated Humoral (antibody-mediated)
Function Activate macrophages and Activate B-cells, promote
cytotoxic T-cells class-switching
Substances secreted IL-2, IFN-γ, lymphotoxin β IL-4, 5, 10, & 13
Result Cytotoxicity; delayed Secretion of antibodies
hypersensitivity
*Inactivated (killed or component) viral vaccines primarily generate a humoral immune
response against extracellular viral antigens, preventing viral entry into the cell. In contrast,
live attenuated viral vaccines can generate a strong cell-mediated immune response that can
kill virally-infected cells, in addition to providing humoral immunity.
*Inactivated versions of the influenza vaccine stimulate the formation of neutralizing
antibodies against the hemagglutinin antigen of included strains. Subsequent exposure to
a strain of influenza included in the vaccine will not result in infection because the antibodies
bind to hemagglutinin, thereby preventing hemagglutinin from attaching to the sialic acid
receptor on host respiratory epithelial cells (preventing viral entry).
*influenza Annual vaccination is recommended due to waning effectiveness over time and
because circulating strains of influenza change from year to year. All individuals age >6
months should be immunized, especially health care workers and those at risk of serious
complications such as the elderly, patients with chronic illness (eg, chronic obstructive
pulmonary disease), and immunocompromised individuals.
*When a multivalent antigen comes in contact with the cell, multiple IgE antibodies become
cross-linked, resulting in aggregation of the FcεRI receptors on the mast cell surface. This
clumping of receptors leads to the activation of non-receptor tyrosine kinases, triggering an
intracellular cascade that ultimately results in mast cell and basophil degranulation.
*Myeloperoxidase is found predominately in neutrophils. Serum levels of myeloperoxidase can
increase following inflammation and infection but would not rise in response to an acute
allergic reaction.
*Anaphylaxis is a systemic type 1 hypersensitivity reaction characterized by increased vascular
permeability and multisystem edema, leading to massive shifting of intravascular fluid to the
extravascular compartment. Symptoms often begin within seconds to minutes after
intravascular exposure to an inciting factor (eg, insect stings, intravenous medications) but can
take up to 2 hours to develop with orally ingested antigens.
*Acute cellular rejection is mediated by host T-lymphocyte sensitization against graft
(foreign) MHC antigens, and it is characterized by a dense infiltrate of mononuclear cells
(eg, lymphocytes) affecting the renal interstitium, tubules, and arterial intima.
*A radioimmunoassay is a laboratory technique that uses specific antibodies and a known
quantity of radiolabeled antigen to determine the amount of antigen present in an unknown
sample. In this technique, specific antibodies against a known antigen are attached to an
assay plate. Next, a fixed quantity of radiolabeled antigen and varying quantities of
unlabeled antigen are added to the plate. The system is subsequently washed to remove
unbound antigens, and radioactivity is measured.
*Primary ciliary dyskinesia
Patients with PCD experience recurrent respiratory infections (eg, chronic sinusitis,
bronchiectasis) as a result of impaired mucociliary clearance. In addition, impaired ciliary
movement during embryogenesis can cause situs inversus (reversed right/left positioning of
internal organs). Infertility in men (impaired sperm motility) and women (immobility of
fallopian tube cilia) is another frequent manifestation.
*Class I HLA proteins (eg, HLA B27) are expressed by all nucleated cells and present
endogenous antigens to CD8+ cytotoxic T cells. By contrast, HLA class II proteins (eg, DR, DP,
DQ alleles) are expressed by antigen-presenting cells (eg, macrophages, dendritic cells) and
present predominantly foreign antigens to CD4+ helper T cells.
*Ankylosing spondylitis, reactive arthritis, arthritis associated with inflammatory bowel disease,
and psoriatic arthritis are seronegative spondyloarthropathies, so-called due to the
absence of serum rheumatoid factor.
*IL-10 reduces production of proinflammatory TH1 cytokines (IL-2 and interferon gamma) and
major histocompatibility complex class II expression (important for antigen presentation and T-
helper cell response). It also inhibits activated dendritic cells and macrophages
*Once given, anti-Rh(D) antibodies bind to Rh-positive fetal erythrocytes that enter the
maternal circulation, preventing their interaction with the maternal immune system via
sequestration and elimination by the mother's spleen.
*When an Rh-negative mother becomes pregnant with an Rh-positive fetus, fetal red blood
cells can enter the maternal circulation and elicit a maternal IgG antibody response with
formation of memory B-lymphocytes (Rh alloimmunization). The risk of transplacental
fetomaternal blood exchange increases with gestational age and is highest during delivery.
After Rh alloimmunization occurs, subsequent pregnancies with Rh-positive fetuses will be at
risk for hemolytic disease of the newborn.
*Th2 cells are involved in humoral immunity and defense against extracellular parasites
*Th1 cells are central to cell-mediated immunity.
*Acute hemolytic transfusion reactions are an example of an antibody-mediated (type II)
hypersensitivity reaction. Anti-ABO antibodies (mainly IgM) in the recipient bind the
corresponding antigens on transfused donor erythrocytes, leading to complement activation.
Anaphylatoxins (C3a and C5a) cause vasodilatation and symptoms of shock, while formation of
the membrane attack complex (C5b-C9) leads to complement-mediated cell lysis.
Hemolytic disease of the newborn due to Rh-incompatibility is another example of type II
hypersensitivity.
*Cytotoxic CD8+ T-lymphocytes are responsible for destroying cells infected with intracellular
pathogens (eg, viruses).
*neutrophils eventually migrate out of the vasculature by squeezing in between the cells via
integrin attachments and adherence to platelet endothelial cell adhesion molecule 1
(PECAM-1). This protein is found primarily at the peripheral intercellular junctions of
endothelial cells
*Deficiency of complement components C1, C2, and C4 leads to increased susceptibility to
infections and systemic lupus erythematosus-like disease. Low levels of C5, C6, C7, C8, and
C9 predispose individuals to infections with Neisseria gonorrhea and N meningitidis.
*Development of fungemia in HIV patient
Candida is a component of normal human skin and mucous membrane flora and is an
opportunistic pathogen (does not cause disseminated infection in healthy people). Host
defense is provided by 2 immune system components with distinct functions:
w. T lymphocytes (in particular TH cells) are important for prevention of
superficialCandida infection (eg, oral/esophageal candidiasis, cutaneous candidiasis,
Candida vulvovaginitis). Conditions such as HIV (low T-cell count) increase the risk of
superficial candidiasis.
x. Neutrophils prevent the hematogenous spread of Candida. Disseminated candidiasis
(eg, candidemia, endocarditis) is more likely in patients who are neutropenic or otherwise
immunocompromised (eg, cancer with chemotherapy) and in those with inherited
impairments of phagocytosis.
The interplay of these 2 components can be seen in patients with HIV. These patients
frequently have superficial Candida infections given their low T-cell counts, but they do not
typically suffer from disseminated candidiasis as a result of HIV itself. If they also have
neutropenia, there is a risk for both localized and disseminated candidiasis.