U WORLD (Step 1) – ALLERGY/IMMUNOLOGY + IMMUNOLOGY (EDUCATIONAL OBJECTIVES)

Last Updated: Feb 15 2020

Disclaimer:
These notes are made only for the sole purpose of rapid revision & overview of a particular system.
It is highly recommended to buy online UW subscription, as new questions & explanations are updated on
daily basis.

Note:
UW has given Allergy/Immunology as a separate system.
Where as Immunology is a part of every organ system.
In this file, I clubbed both of them so as to have over all idea of Immunology.
- Dr Zaki

T – Indicates this explanation has a Table/Flow Chart.

F – Indicates this explanation has a Diagram.

1
 GENERAL
Immunology - Principles

746 (T)
MHC Class I
• CD8+ cells recognize foreign antigens presented with MHC class I proteins.
• Each MHC class I molecule consists of a heavy chain and a β2-microglobulin.

12299 (F)
Radio Immuno Assay (RIA)
• RIA uses specific antibodies & a fixed quantity of radiolabelled antigen to determine the
amount of antigen present in an unknown sample.
• This is done by measuring the amount of radiolabeled antigen displaced from antibodies in
the system.

SPLEEN
Asplenia

732
• Spleen acts as both
✓ A blood filter capable of removing circulating pathogens
✓ As a major site of opsonizing antibody synthesis.
• Asplenic patients are prone to infections caused by encapsulated organisms such as
✓ Strepto pneumoniae
✓ Haemophilus influenzae
✓ Neisseria meningitidis

2
 IMMUNITY
Immunity - Cell Mediated

298 (F)
Fas
• The Fas receptor acts to initiate the extrinsic pathway of apoptosis.
• Mutations having the Fas receptor or Fas ligand can prevent apoptosis of autoreactive
lymphocytes, thereby increasing the risk of auto-immune disorders such as SLE.

558 (F)
Negative selection
• The process of negative selection in T cell maturation is essential for eliminating T cells that
bind to self MHC or self antigens with overly high affinity.
• This process occurs in the thymic medulla.
• If these cells were permitted to survive, they would likely induce immune and inflammatory
reactions against self antigens leading to autoimmune disease.

559
Immature T-lymphocytes
• Immature T-lymphocytes express both the CD4 and CD8 cell surface antigens in addition to
a complete TCR or a pro-TCR.
• These lymphocytes exist in the thymic cortex where they undergo positive selection
and in the thymic medulla where they undergo negative selection.

745
NK cells
• NK cells recognize and kill cells with decreased MHC class I antigen cell surface expression,
such as virus-infected cells and tumor cells.
• They are large lymphocytes that contain perforins and granzymes in cytoplasmic granules.
• NK cells kill target cells by inducing apoptosis.

750 (F)
Eosinophils
• Eosinophils play a role in host defense during parasitic infection.
• When stimulated by antibodies bound to a parasitic organism, they destroy the parasite via
antibody-dependent cell-mediated cytotoxicity with enzymes from their cytoplasmic
granules.
• Another function of eosinophils is regulation of type I HSR.

762 (T)
IL-12
• IL-12 stimulates the differentiation of "naïve" T-helper cells into the TH1 subpopulation.
• Patients with IL-12 receptor deficiency suffer from severe mycobacterial infections due to
the inability to mount a strong cell-mediated granulomatous immune response.
• They are treated with IFN-γ.

3
1756
Capsases
• Apoptosis can occur through either
✓ Intrinsic (mitochondria mediated) pathway or
✓ Extrinsic (receptor initiated) pathway.
• Both pathways converge in activation of caspases.
• Capsases are proteolytic enzymes that cleave cellular proteins.

Immunity - Humoral
1614
Isotype Switching
• The primary immune response to a new antigen initially results in plasma cells that only
produce IgM.
• Isotype switching later occurs in the germinal centers of lymph nodes and requires
interaction of the CD40 receptor on B-cells with the CD40 ligand (CD154) expressed by
activated T-cells.
• IgG is the main serum immunoglobulin of the secondary response.

Sarcoidosis
797
• Sarcoidosis is characterized by noncaseating granulomas due to dysregulated cell-mediated
immunity.
• Activated antigen-presenting cells produce IL-12, which stimulates the differentiation of
Th1-type CD4+ cells.
• Th1 cells produce IL-2 and interferon-γ, which stimulate Th1 cell proliferation and
macrophage activation, respectively.

4
 MHC
MHC
542 (F)
MHC Class II
• MHC Class II is expressed on the surface of antigen presenting cells (APC)
• And presents extracellular antigens to T cells after extracellular protein is degraded within
acidified lysosomes.
• Failure to acidify lysosomes would lead to deficient expression of MHC Class II bound to
foreign antigen and subsequent lack of interaction between APCs and T-cells.

17446 (F)
MHC class I
• Transporter a/w antigen processing (TAP) proteins are necessary for loading of cytoplasmic
(viral) proteins onto MHC class I molecules.
• MHC class I – peptide complex can then activate CD8+ cytotoxic T cells through interaction
with T cell receptor & CD8 Co-receptor.

17447
MHC class II
• MHC class II molecules are encoded by HLA-DP, HLA-DQ, HLA-DR genes
• And present extracellular antigens processed in acidified lysosomes by APCs (B cells,
Macrophages).
• Absence of MHC class II expression impairs activation of B & T cells, resulting in a form of
SCID.

5
 HLA SUBTYPES
Ankylosing Spondylitis
752
• Sero Negative Spondylo Arthropathies (SNSA) include
✓ Ankylosing Spondylitis
✓ Reactive arthritis
✓ Psoriatic arthritis
✓ Arthritis a/w inflammatory bowel disease
• Individuals expressing HLA B27 are at increased risk for SNSA.

Reactive Arthritis
743 (T)
• The classic triad of reactive arthritis is
✓ Nongonococcal urethritis
✓ Conjunctivitis
✓ Arthritis
• It is an HLA-B27-associated arthropathy that occurs within several weeks following a
genitourinary or enteric infection.
• It belongs to the group of SNSA (including ankylosing spondylitis) and can cause sacroiliitis
in about 20% of cases.

Rheumatoid Arthritis
754 (T)
• Rheumatoid arthritis results from an immune response directed against autoantigens in
joints.
• Infiltrating CD4+ T cells secrete cytokines that promote inflammatory synovitis.
• They also stimulate
✓ B cells to produce rheumatoid factor (IgM antibody specific for Fc component of IgG) &
✓ Anti citrullinated protein antibodies that contribute to chronic inflammation & joint
destruction.

6
 IMMUNO GLOBULINS
Immuno Globulins
539 (F)
Fc
• The carboxy terminal of the Fc portion of the heavy immunoglobulin chains represents the
site that binds to the Fc receptors on neutrophils and macrophages.
• Antibody bound to antigen is able to signal for the phagocytosis of that antigen by a
conformational change of the Fc region allowing binding to the Fc receptor on phagocytes.
• This leads to subsequent phagocytosis of the organism / antibody complex and subsequent
destruction of the organism.

540 (F)
IgM
• The classical complement cascade begins with binding of the C1 complement component to
either two molecules of IgG or to two molecules of IgM.
• Because IgM circulates in pentameric form, it is a much better activator of the complement
system.
• The C1 molecule binds to the Fc region of the heavy immunoglobulin chain in the region
near the hinge point.

1467 (F)
IgA
• The live attenuated oral (Sabin) poliovirus vaccine produces a stronger mucosal secretory
IgA immune response than does the inactivated poliovirus (Salk) vaccine.
• This increase in mucosal IgA offers immune protection at the site of viral entry by inhibiting
attachment to intestinal epithelial cells.

Multiple Myeloma (MM)

15466
• Multiple myeloma is a/w clonal proliferation of plasma cells in the bone marrow.
• This prevents normal B-cell lymphogenesis and increases the risk of bacterial infection due
to decreased production of normal immunoglobulins.

7
 COMPLEMENT
Complement Deficiency
739
• Deficiency of complement factors that form the MAC - membrane attack complex (ie C5b –
C9) results in recurrent infections by Neisseria species.

Angioedema
1612 (T)
• Angioedema can be
✓ Hereditary (autosomal dominant)
✓ Acquired (a/w ACE inhibitors)
• In hereditary angioedema, low C1 esterase inhibitor activity leads to ↑ in bradykinin
activity.
• ACE inhibitors should not be used in these patients.

11667
• C1 Inhibitor (C1 INH) deficiency causes ↑ cleavage of C2 & C4 & results in inappropriate
activation of complement cascade.
• C1 INH also blocks Kallikrein – induced conversion of Kini-Nogen To Bradykinin, a potent
vasodilator a/w angioedema.

Pharyngitis
11677 (F)
• Opsonization occurs when host proteins such as immunoglobulins or complement bind to
foreign cells such as bacteria and coat the surface, enhancing phagocytosis.
• The most important opsonins (coating proteins) are
✓ Immunoglobulin G
✓ Complement C3b

8
 CYTOKINES

Cytokines

1468 (F)
Interferons α and β
• Interferons α and β are produced by most human cells in response to viral infections.
• The production of α and β interferons helps suppress viral replication by halting protein
synthesis and promoting apoptosis of infected cells, limiting the ability of viruses to spread
through the tissues.
8530 (F)
IL-2
• Interleukin-2 (IL-2)
✓ Is produced by helper T cells
✓ Stimulates the growth of CD4+ and CD8+ T cells and B cells.
• IL-2 also activates natural killer cells and monocytes.
• The ↑ activity of T cells and natural killer cells is thought to be responsible for IL-2’s anti-
cancer effect on metastatic melanoma and renal cell carcinoma.

Inflammation

1800 (T)
• Leukotriene B4 stimulates neutrophil migration to sites of inflammation.
• Other important chemotactic agents include
✓ 5-HETE (leukotriene precursor)
✓ Complement component C5a
✓ IL-8
8480
• Inflammation is characterized by the passage of circulating inflammatory leukocytes into
the inflamed tissue.
• The steps involved include
✓ Margination
✓ Rolling
✓ Activation
✓ Tight adhesion and crawling
✓ Transmigration

8539 (F)
IL-8
• Interleukin-8 is a chemokine produced by macrophages that induces chemotaxis and
phagocytosis in neutrophils.
• Other significant chemotactic agents include
✓ N-formylated peptides
✓ Leukotriene B4
✓ 5-HETE (the leukotriene precursor)
✓ Complement component C5a

9
Inflammatory Bowel Disease
1597 (F)
IL-10
• Of the cytokines released in the setting of tissue injury, IL-10 plays important anti-
inflammatory and immunomodulatory roles, especially in the pathogenesis of inflammatory
bowel disease.
• IL-10 attenuates the immune response through
✓ Inhibition of TH1 cytokines
✓ Reduction of MHC Class II expression
✓ Suppression of activated macrophages and dendritic cells
14805
Adalimumab
• Adalimumab is a recombinant human IgG that binds TNF – Alpha.
• Anti drug antibodies can develop against adalimumab (or other immunoglobulin based anti
TNF agents) that can block its interaction with TNF Alpha, preventing the drug from
functioning & leading to more rapid drug clearance.

Tuberculosis
301
• T-helper subtype 1 cells release interferon-gamma leading to the activation of
macrophages, a process critical for control of Mycobacterium tuberculosis infection.
• Activated macrophages form mature phagolysosomes that destroy phagocytosed
mycobacteria and can differentiate into epithelioid and Langerhans giant cells to wall off
extracellular mycobacteria within caseating granulomas.
• Interferon-γ, IL-12, and TNF-α are critical cytokines for the formation and maintenance of
granulomas.
1218 (F)
• Mycobacteria tuberculosis primarily replicates within the phagosome, leading to display of
mycobacterial antigens on MHC class II molecules.
• This results in the activation of CD4 cells and subsequent control of the infection with
macrophages.
1220
• Mycobacterium tuberculosis triggers CD4 T lymphocytes to release interferon-gamma,
which leads to macrophage activation (improves intracellular killing ability) and
differentiation into epithelioid histiocytes.
• These cells, along with horseshoe-shaped, multinucleated Langhans giant cells (fused,
activated macrophages) are a key component of granuloma formation.
1598
• The caseating granulomas of tuberculosis are almost always surrounded by large epithelioid
macrophages with pale pink granular cytoplasm.
• CD14 is a surface marker of the monocyte-macrophage cell lineage.

11525
• IFN – Gamma release assays test for latent TB infection by measuring the amount of IFN –
Gamma released by T lymphocytes when exposed to antigens unique to MTB.

10
 VACCINATION/IMMUNIZATION

Diphtheria

1388 (T)
• The primary treatment for diphtheria is diphtheria anti-toxin (passive immunization), which
inactivates circulating toxin.
• Antibiotics should also be administered to reduce continued production of toxin.

Tetanus

760
Neurotoxin Tetano-Spasmin
• Clostridium tetani produces the neurotoxin tetano-spasmin,
✓ which blocks inhibitory neuro-transmission in spinal cord &
✓ leads to tonic muscular contraction.
• Tetanus is prevented by immunization with an inactivated toxoid that triggers the
production of anti-toxin antibodies (Active Immunity).

Immunizations

965 (T)
Haemophilus influenzae serotype b vaccine
• The Haemophilus influenzae serotype b vaccine consists of a capsular polysaccharide
conjugated to a carrier protein (tetanus toxoid [TT] protein or outer membrane protein
[OMP] of Neisseria meningitidis).
• Protein conjugation causes a T cell-mediated immune response leading to long-term
immunity through production of memory B-lymphocytes.

1466 (F)
• Inactivated (killed or component) viral vaccines primarily generate a humoral immune
response against extra-cellular viral antigens, preventing viral entry into cell.
• Live attenuated viral vaccines can generate a strong cell mediated immune response that
can kill virally infected cells, in addition to providing humoral immunity.

11872 (F)
Pneumococcal conjugate vaccine
• Pneumococcal conjugate vaccines are strongly immunogenic in infancy due to both B and T
cell recruitment.
• They provide higher, longer-lasting antibody titers relative to pneumococcal polysaccharide
vaccines.
• The pneumococcal polysaccharide vaccine is poorly immunogenic in infants due to their
relatively immature humoral antibody response.

11
Epiglottitis

967 (F)
• Acute epiglottitis
✓ Rapidly progressing fever
✓ Severe sore throat
✓ Drooling & progressive airway obstruction
✓ Potentially accompanied by stridor
• This illness is MCC by H. influenzae type b,
but the Hib vaccine has dropped the incidence of this disease considerably.
• H. influenzae type b can still cause disease in unimmunized or improperly immunized patients
as well as fully immunized patients in some cases.

Rh Allo Immunization

545 (F)
Hemolytic disease of the newborn
• MC occurs from maternal sensitization to Rh antigens during a prior pregnancy with an
Rh(D)+ fetus.
• In subsequent Rh(D)+ pregnancies, maternal anti-Rh(D) IgG antibodies cross the placenta
and cause a severe autoimmune hemolytic anemia in the fetus and life-threatening hydrops
fetalis.

1683 (F)
Anti-Rh immune globulin
• Anti-Rh immune globulin consists of IgG anti-D antibodies that opsonize Rh+ fetal
erythrocytes, promoting clearance by maternal reticuloendothelial macrophages and
preventing maternal Rh sensitization.
• It is routinely administered to Rh-negative women at 28 weeks gestation and immediately
postpartum.

8261 (T)
• With maternal blood types A and B, erythroblastosis fetalis and hemolytic disease of the
newborn do not occur, as the naturally occurring antibodies (anti-A and -B) are of the IgM
type and cannot cross the placenta.
• In contrast, in type O mothers, the antibodies are predominantly IgG and can cross the
placenta to cause fetal hemolysis.

12
 HYPER SENSITIVITY
Asthma

526 (F)
• An excess of Th2 cell activity relative to Th1 cell activity may underlie the pathogenesis of
asthma.
• In the asthma sensitization phase,
inhaled antigens stimulate Th2 cells to secrete IL-4 & IL-13, which together promote B-
lymphocyte class switching for IgE synthesis, leading to mast cell priming.
• Th2 cells also secrete IL-5, which activates eosinophils.

Anaphylaxis

1366
• Anaphylactic shock:
✓ Vasodilation
✓ Increased Vascular Permeability
✓ Broncho Constriction
• Epinephrine counteracts these physiological mechanisms & is the drug of choice for
treatment of anaphylaxis.

2068 (T)
Tryptase
• Anaphylaxis is the result of widespread mast cell and basophil degranulation and the
release of preformed inflammatory mediators, including histamine and tryptase.
• Tryptase is relatively specific to mast cells and can be used as a marker for mast cell
activation.

2069 (F)
High-affinity IgE receptor (FcεRI)
• FcεRI
✓ Is found on the surface of mast cells and basophils
✓ Normally binds the Fc portion of circulating IgE antibodies.
• Cross-linking of multiple membrane-bound IgE antibodies by a multivalent antigen results in
aggregation of the FcεRI receptors, causing degranulation and the release of preformed
mediators (eg, histamine, tryptase) that initiate an allergic response.

Latex Allergy
759 (F)
IL-4
• IL-4 is produced by the TH2 subset of T-helper cells.
• It facilitates proliferation of B-cells and TH2 lymphocytes, and stimulates antibody isotype
switching to IgE which mediates type 1 HSR (Allergic)

13
Serum Sickness

741 (T)
• Serum sickness is Type III HSR to non-human proteins.
• Characterized by vasculitis resulting from tissue deposition of circulating immune
complexes.
• Clinical Findings:
✓ Fever
✓ Pruritic skin rash
✓ Arthralgias
✓ Low serum C3, C4 complement levels

Hypersensitivity Reactions

544
• Type IV (Delayed) HSR:
✓ Contact dermatitis
✓ Candida extract skin reaction
• Characterized by
✓ Erythema
✓ Induration
that develops 24-48 hrs after repeat exposure to an antigen
• T lymphocytes mediate the inflammation in these reactions through
✓ Cytokine release
✓ CD8+ cytotoxicity
✓ Macrophage recruitment

556
Wheal-and-flare lesions
• Wheal-and-flare lesions usually result from allergic (type I HSR) reactions.
• On initial exposure, an allergen (eg, insect venom) promotes antibody class switching to IgE.
• Subsequent exposure promotes cross-linking of IgE on basophils and mast cells, resulting in
degranulation and release of multiple vasoactive mediators, including histamine.

747 (T)
• Acute hemolytic transfusion reaction is a antibody-mediated (type II) HSR caused by pre-
existing anti-ABO antibodies that bind antigens on transfused donor erythrocytes.
• Subsequent complement activation results in
✓ Erythrocyte lysis
✓ Vasodilation
✓ Symptoms of shock
• Common findings:
✓ Fever
✓ Hypotension
✓ Chest and back pain
✓ Hemoglobinuria

14
1131
• Type 1 HSR
✓ Are mediated by interaction of allergen with pre-existing IgE bound to basophils & mast
cells.
✓ This facilitates cross-linking of the surface IgE molecules that signals the cell to
degranulate releasing chemical mediators (eg, histamine, heparin).
✓ These agents are responsible for the immediate signs & symptoms of allergy, from a
local wheal & flare to life-threatening anaphylaxis.

1133 (F)
Poison Ivy Dermatitis
• Is a form of allergic contact dermatitis, which is a type IV HSR mediated primarily by T
lymphocytes.
• It manifests as intensely pruritic erythematous papules, vesicles or bullae that often form
linear patterns.

2079
Candidal Antigen Skin Test
• Assesses the activity of T cell-mediated immunity through the recruitment of macrophages
and CD4+ and CD8+ T lymphocytes in a type IV HSR.
• Anergy, or failure to respond to candida antigen testing, is typical in patients with SCID.

PSGN

567 (T)
PSGN
• Is the MCC of nephritic syndrome (eg, hematuria, edema, hypertension) in children,
• Typically occuring 2-4 weeks after a streptococcal infection (eg, impetigo, cellulitis,
pharyngitis).
• It is caused by a type III (immune-complex–mediated) HSR resulting from nephritogenic
strains of group A beta-hemolytic Streptococcus.

Anti Histamines

174
• 1st generation AH can cause significant side effects due to blockade of
✓ Cholinergic
✓ Alpha adrenergic
✓ Serotonergic pathways
• They should be avoided in older patients with cognitive or functional impairments.

15
 BLOOD TRANSFUSION
Blood Transfusion

17780 (T)
Delayed Hemolytic Transfusion Reactions
• Are usually mild, hemolytic reactions that occur >24 hours after blood transfusion.
• They are a type of anamnestic response (delayed immunologic response) that occurs in
patients previously exposed to a minor RBC antigen (previous blood transfusion,
pregnancy).

AUTO ANTIBODIES

Granulomatosis with Polyangiitis

459
• Characteristic of granulomatosis with polyangiitis (Wegener’s)
✓ Necrotizing vasculitis of upper & lower respiratory tract (causing nasal ulcerations,
sinusitis, hemoptysis)
✓ RPGN – producing a variable degree of renal failure
• This disease is a/w C-ANCAs, which may target neutrophil proteinase 3.

SLE

761 (T)
• Anti-Nuclear Antibodies
✓ Are found in almost all patients with SLE
✓ But are also found in many other auto-immune disorders & have low specificity.
• Anti dsDNA & Anti Smith Antibodies have lower sensitivity but higher specificity.

16
 IMMUNO DEFICIENCIES

Primary Immuno Deficiency Disorders

538 (T)
Leukocyte Adhesion Deficiency (LAD)
• Is due to absence of CD18 antigens necessary for formation of integrins.
• Clinical features are caused by failure of leukocyte chemotaxis & include
✓ Recurrent skin & mucosal infections without purulence
✓ Delayed separation of umbilical cord
✓ Persistent leucocytosis

557
Chronic Granulomatous Disease
• Is an X-linked disorder
• Resulting from deficiency of NADPH oxidase, the enzyme responsible for formation of
reactive oxygen species in phagosomes.
• Neutrophils affected by this disorder are unable to kill catalase-producing organisms,
resulting in recurrent bacterial and fungal infections that frequently involve the
✓ Lungs
✓ Skin
✓ Lymph nodes

571 (T)
Chronic Granulomatous Disease (CGD)
• Is MC due to an X-linked mutation affecting NADPH oxidase.
• Deficiency of this enzyme leads to an inability of neutrophils to form the oxidative burst
necessary to kill organisms in their phagolysosomes.
• CGD can be diagnosed by
✓ Absence of the normal blue (Nitroblue Tetrazolium Test)
✓ Absence of fluorescent green pigment (Dihydro Rhodamine Flow Cytometry Test)

1441 (T)
Chronic Granulomatous Disease (CGD)
• CGD results from a genetic defect in NADPH oxidase.
• Normally, NADPH oxidase participates in the killing of microbes within neutrophil and
macrophage phagolysosomes.
• Patients with CGD develop recurrent bacterial and fungal infections that are predominantly
caused by 5 catalase-positive organisms:
✓ Staphylococcus aureus
✓ Burkholderia cepacian
✓ Serratia marcescens
✓ Nocardia
✓ Aspergillus

17
2078 (T)
SCID
• Is caused by a genetic defect in T cell development, leading to loss of both cellular and
humoral immunity.
• Patients present in infancy with recurrent bacterial, viral, fungal, and opportunistic
infections as well as failure to thrive and chronic diarrhea.

8384 (F)
Interferon-Gamma Signaling Pathway
• Inherited defects involving the interferon-gamma signaling pathway result in disseminated
mycobacterial disease in infancy or early childhood.
• Patients require lifelong treatment with antimycobacterial agents.

8532 (F)
• DiGeorge syndrome
✓ Causes an extreme deficiency in the number of mature T lymphocytes, leading to poor
development of the lymph node paracortex.
• Agamma Globulinemia
✓ Causes an absence of B cells, preventing primary lymphoid follicles and germinal centers
from forming in the lymph node cortex.

X Linked Agamma Globulinemia

1134 (F)
X-linked (Bruton) Agamma Globulinemia
• Is caused by a defect in B cell maturation, resulting in the absence of mature B cells with
severe deficiency of all immunoglobulin types.
• T cell numbers and function remain intact.
• Due to the absence of B cells, primary lymphoid follicles and germinal centers will not form
within lymph nodes.

Selective IgA Def

1130 (T)
• Selective IgA deficiency
✓ MC primary immune deficiency
✓ Can present with recurrent sinopulmonary & GI infections as well as autoimmune
disease.
✓ Patients with severe IgA deficiency can have anaphylaxis during transfusion of blood
products that contain small amounts of IgA.

18
Hyper IgM Syndrome

541 (T)
• Hyperimmunoglobulin M (hyper-IgM) syndrome results from defective immunoglobulin
class switching due to a defect in CD40 ligand-CD40 interaction.
• Absence of the CD40 ligand is the MCC and is inherited in an XLR pattern.
• Clinical features: Recurrent
✓ Sino Pulmonary
✓ Gastrointestinal
✓ Opportunistic infections

SCID

561
• The 2nd MCC of SCID is autosomal recessive deficiency of Adenosine Deaminase, an enzyme
necessary for the elimination of excess adenosine within cells.
• Toxic levels of adenosine accumulate within lymphocytes in this condition, leading to
lymphocyte cell death and resultant cellular and humoral immune deficiency.
• Patients with this condition can be treated with hematopoietic cell transplantation or gene
therapy.

1995 (T)
• SCID is characterized by combined T and B cell dysfunction.
• It is a life-threatening condition that presents in infancy with
✓ Severe bacterial and viral infections
✓ Mucocutaneous candidiasis
✓ Persistent diarrhea
✓ Failure to thrive
• Laboratory findings:
✓ Absent T cells
✓ Hypo Gamma Globulinemia
• The thymic shadow is not usually present due to severe T cell deficiency.

15293 (F)
Adenosine deaminase (AD) inhibition/absence
• AD inhibition/absence is highly lympho-cytotoxic.
• Medications that block ADA are used to treat lymphocyte-derived cancers.
• Inherited gene mutations in ADA lead to autosomal recessive (AR) disease of SCID.

19
Wiskott Aldrich Syndrome

537
• Triad of
✓ Eczema
✓ Thrombocytopenia
✓ Combined B-lymphocyte and T-lymphocyte deficiency.
• Onset of disease is early in life with thrombocytopenia present at birth and eczema and
repeated infections, particularly by encapsulated organisms, following at 6 to 12 months of
age.

Chediak Higashi Syndrome

1132
• AR disorder of neutrophil phagosome lysosome fusion
• Results in
✓ Neurologic abnormalities
✓ Partial albinism
✓ Immunodeficiency caused by defective neutrophil function

20
 TRANSPLANT REJECTION
Transplant Rejection

546 (T)
• Organ rejection can be
✓ Hyperacute
✓ Acute
✓ Chronic
• Acute Cellular Rejection
✓ Most often occurs within weeks or up to 6 months after transplant
✓ Is predominantly cell mediated, involving sensitization of host T lymphocytes against
donor MHC antigens.
✓ There is typically graft dysfunction with histology showing a dense, mononuclear
(lymphocytic) infiltrate.

569 (T)
Hyperacute Rejection
• Is caused by preformed antibodies in the recipient that recognize & attack donor antigens
(type II HSR).
• These are often anti – ABO blood group or anti – HLA antibodies.
• Vascular injury & capillary thrombotic occlusion lead to rapid ischemic necrosis of renal
graft, often evidenced by gross cyanosis & mottling immediately following graft perfusion.

744 (T)
Chronic Renal Allograft Rejection
• Manifests months to years after a transplant
• Presents with worsening HTN & a gradual decline in renal function.
• It involves a chronic, antibody – mediated response against donor antigens &
• Leads to obliterative vascular wall thickening, tubular atrophy, interstitial fibrosis.
• The process is usually irreversible & eventually leads to graft failure.

11786 (F)
Sirolimus
• Sirolimus binds to the immunophilin FK-506 binding protein (FKBP) in the cytoplasm, forming
a complex that binds and inhibits mTOR.
• Inhibition of mTOR signaling blocks IL-2 signal transduction and prevents cell cycle
progression and lymphocyte proliferation.

21
Transplantation - Heart
568
• Acute Cardiac Transplant Rejection
✓ Occurs weeks following transplantation & is primarily a cell-mediated process.
✓ On histopathologic analysis of an endomyocardial biopsy, a dense mononuclear
lymphocytic infiltrate with cardiac myocyte damage will be visualized.
✓ Treatment with immunosuppressive drugs is aimed primarily at preventing this form of
rejection.

Transplantation - Lung
534 (T)
Chronic Lung Transplant Rejection
• Is due primarily to progressive scarring of the small airways, leading to bronchiolitis
obliterans.
• Manifestations occur months or years after transplantation and include obstructive lung
disease (eg, reduced FEV1) with dyspnea and dry cough.

Graft Vs Host Disease

1613
• GVHD can occur following transplantation of organs rich in lymphocytes (liver).
• T lymphocytes found in donor organ become sensitized against the MHC antigens of
recipient & subsequently attack the host’s tissues.
• The skin, liver, GI tract are most frequently affected.

IMMUNO - DRUGS
Calci Neurin Inhibitors
1155 (F)
• Calcineurin is an essential protein in the activation of interleukin-2, which promotes the
growth and differentiation of T cells.
• Immunosuppressants such as cyclosporine and tacrolimus work by inhibiting calcineurin
activation.

Immuno Therapy
12048 (F)
Programmed Cell Death Protein 1 (PD-1)
• The binding of Programmed Cell Death Protein 1 (PD-1) to one of its ligands (Programmed
Death-Ligand 1 [PD-L1]) downregulates the immune response by inhibiting cytotoxic T
cells.
• Many types of cancers evade immunodetection by ↑ expression of PD-L1 on their surface.
• Monoclonal antibodies against PD-1 upregulate the T-cell response and promote tumor cell
apoptosis.

22
 MISCELLANEOUS
Toxic Shock Syndrome

676 (F)
• Super Antigens (TSS toxin) interact with MHC molecules on APCs & the variable region of T
lymphocyte receptor to cause nonspecific, widespread activation of T cells.
• This results in release of IL-2 from T cells & IL 1 & TNF from macrophages.
• This immune cascade is responsible for manifestations of TSS.

15509 (F)
TSS
• Is typically a/w prolonged use of tampons or wound packing, which allows Staph aureus to
replicate locally & release pyrogenic toxic superantigens (TSS toxin 1) into blood.
• Superantigens bind to MHC II complex of APCs without processing & non specifically
activate T cells.
• This leads to dramatic release of inflammatory cytokines, which causes manifestations of
disease (hypotension, high fever, organ failure, diffuse, erythematous rash).

Febrile Neutropenia
112
• Local defense against Candida is performed by T cells,
whereas systemic infection is prevented by neutrophils.
• For this reason, localized candidiasis is common in patients who have HIV, but neutropenic
individuals are more likely to have the systemic form of disease.

Henoch Schonlein Purpura

458
• Small vessel leukocytoclastic angiitis a/w IgA & C3 deposition is typical of HSP.
• HSP
✓ Is MC in children 3 to 11 years old & is most often related to a recent infection.
✓ Most children present with
➢ Palpable skin lesions
➢ with or without abdominal pain & arthralgias.
✓ Although usually self-limiting, patients afflicted with HSP should be observed carefully
because glomerulo-nephritis & even end stage renal disease are possible complications.
758 (T)
Henoch-Schönlein Purpura (HSP)
• Is an IgA-mediated type III HSR in children that generally follows infection.
• Deposition of circulating IgA-containing immune complexes in small vessels results in
systemic vasculitis.
• Common manifestations:
✓ Palpable lower-extremity purpura
✓ Abdominal pain
✓ Arthralgias
✓ Hematuria

23
Hepatitis B

380 (T)
• The presence of anti-HBc & anti HBs antibodies in serum without detectable viral antigens
indicates recovery from acute hepatitis B infection.
• In contrast, patients vaccinated against hepatitis B will have anti HBs antibodies without
detectable levels of anti HBc.
• Chronic hepatitis B is indicated by persistent levels of HBsAg & HBV DNA in serum.

15177
• Immunization against HBV uses recombinant HBsAg to generate anti-HBs antibodies.
• These antibodies prevent infection by binding to the envelope of circulating virus and
inhibiting viral entry.

Syphilis

7581
Jarisch Herxheimer reaction (JHR)
• JHR is an acute inflammatory reaction that occurs within hours of treatment for spirochetal
(syphilis) infections.
• The rapid lysis of spirochetes releases inflammatory bacterial lipo-proteins into circulation &
cayses acute fevers, rigors, myalgias.

Immotile Cilia Syndrome

1611 (F)
Kartagener syndrome
• Is a form of primary ciliary dyskinesia characterized by the triad of
✓ Situs inversus
✓ Chronic sinusitis
✓ Bronchiectasis
• It occurs due to mutations that impair the structure or function of cilia.
• Cystic fibrosis also causes chronic respiratory infections, but it is not associated with situs
inversus.

Infectious Mono Nucelosis

15490 (F)
Reactive (Atypical) Lymphocytes
• Are activated, pathogen-specific cytotoxic T cells or natural killer cells that form in response
to certain intracellular infections.
• In contrast to normal lymphocytes, reactive lymphocytes are large, scalloped, & have
abundant cytoplasm.
• Reactive lymphocytosis is a diagnostic feature of infectious mononucleosis.

24
Melanoma

16862
• Melanoma lesions often have multiple color variations.
• The different colors represent different activities within the tumor.
• Whitish/gray areas occur when cytotoxic T cells recognize tumor antigens & destroy
malignant cells, leading to melanocyte regression.
• Red areas arise due to vessel ectasia & local inflammation, whereas brown or black areas
are generally due to advancing malignant melanocytes.

16895 (F)
• Programmed death receptor 1 (PD 1) is a checkpoint inhibitor that downregulates the
cytotoxic T cell response.
• Neoplastic cells often exploit this receptor via the overexpression of PD 1 ligand.
• PD 1 receptor inhibitors (Pembrolizumab) restore the T cell response, allowing cytotoxic T
cells to invade the tumor & induce apoptosis of neoplastic cells.

Ubiquitin Proteasome Pathway

11674 (F)
• An essential step in the activation of cellular immune response to a virus is the breakdown
of intra-cellular viral proteins by UPP.
• This pathway is initiated by ubiquitin ligases, which recognize specific protein substrates &
attach a ubiquitin tag.
• The target proteins are then degraded by a proteasome into peptide fragments, which are
coupled with MHC class I proteins & presented on the cell surface for surveillance by
cytotoxic CD8+ lymphocytes.

25