Immunopathology 3 Flashcards by Iseoluwa Ojo

IMMUNODEFICIENCY DISEASES INTRODUCTION

Congenital B-cell defects are clinically conspicuous because of the reduced resistance to ______ infection that they involve.
In contrast, primary T-cell defects leave the patient unprotected against ____________

bacterial

viruses and fungi.

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Patients with a combined B cell and T-cell deficiency are poor candidates for survival.

T/F

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Among the acquired immunodeficiency disorders, gammopathy due to ____________ and AIDS due to __________ warrant special mention.

neoplastic proliferation of a plasma cell clone

infection with the human immunodeficiency virus (HIV)

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Immunodeficiencies can be divided into the primary immunodeficiency disorders, which are almost always _______ determined

And secondary immunodeficiency states, which may arise as complications of _______ factors

genetically

External factors

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Most primary immunodeficiency diseases are genetically determined and affect only INNATE IMMUNITY

T/F

Both INNATE IMMUNITY ACQUIRED IMMUNITY

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Most primary immunodeficiencies manifest themselves in _____, between _____ and ____ of life, and they are detected because _____________________

infancy; 6 months and 2 years

the affected infants are susceptible to recurrent infections.

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PRIMARY IMMUNODEFICIENCY

X-Linked Agammaglobulinemia (____
Agammaglobulinemia)

Due to ______

Bruton’s

disordered B-cell maturation

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In Bruton’s Agammaglobulinemia

Naïve b cells can mature to plasma cells

T/F

Cannot

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Bruton’s Agammaglobulinemia

Caused by mutations in a _______, called __________;

the gene that encodes it is located on the ____ arm of the ___ chromosome at ____.___.

cytoplasmic tyrosine kinase; Bruton tyrosine kinase (Btk)

long; X

Xq21.22

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Bruton’s Agammaglobulinemia

The disease usually does not become apparent until about _____ of age, as _______

6 months

maternal immunoglobulins are depleted.

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Bruton’s Agammaglobulinemia

Recurrent ____s infection (________)

BEG

bacterial IgG, enteroviruses IgA, giardia

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Beware of live attenuated (eg polio) vaccines in patients suffering from Bruton’s Agammaglobulinemia

T/F

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Bruton’s Agammaglobulinemia

Recurrent BEG infection

B Causative Organisms
•———-,———,———

enteroviruses, such as _____,_____,______

Haemophilus influenzae
Streptococcus pneumoniae, or
Staphylococcus aureus.

echovirus, poliovirus, and coxsackievirus

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In Bruton’s Agammaglobulinemia

•B cells are ______________ in the circulation, and the serum levels of all classes of immunoglobulins are _______.

•Pre-B cells, are found in _____ numbers in the bone marrow.

• Germinal centers of ____,______,______, and ___ are underdeveloped.

• Plasma cells are (present or absent?) throughout the body.

• T cell–mediated reactions are ____.

absent or markedly decreased ; depressed

normal

lymph nodes, Peyer’s patches, the appendix, and tonsils

Absent ; normal

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Autoimmune diseases, such as _______ and ______, occur with increased frequency, in as many as 35% of individuals with X-linked agammaglobulinemia disease, which is paradoxical ___________

arthritis and dermatomyositis

in the presence of an immune deficiency

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The treatment of X-linked agammaglobulinemia is ___________

replacement therapy with immunoglobulins.

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Common Variable Immunodeficiency

(Well or Poorly ?) defined entity

The feature common to all patients is _______, generally affecting all the ________ but ____

Poorly

hypogammaglobulinemia

antibody classes

sometimes only IgG.

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Relatives of Common Variable Immunodeficiency patients have a high incidence of __________

selective IgA deficiency

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In contrast to X-linked agammaglobulinemia, most individuals with common variable immunodeficiency have ________ numbers of B cells in the blood and lymphoid tissues.
These B cells, however, are _________

normal or near-normal

not able to differentiate into plasma cells.

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In contrast to X-linked agammaglobulinemia, common variable immunodeficiency affects (male or female?) , and the onset of symptoms is in ______ or _____

both sexes equally

childhood or adolescence

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common variable immunodeficiency

Histologically the B-cell areas of the lymphoid tissues (i.e., lymphoid follicles in nodes, spleen, and gut) are _____.

hyperplastic

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Isolated IgA Deficiency

Most common in the _____ world. It is far less common in _______

westerns; blacks and Asians

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Isolated IgA Deficiency

Characterized by _____ levels of _________

It may be familial, or acquired in association with toxoplasmosis, measles, or some other viral infection

extremely low

both serum and secretory IgA

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The basic defect in isolated IgA deficiency is ______________

impaired differentiation of naive B lymphocytes to IgA-producing cells

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Most individuals with isolated IgA deficiency disease are symptomatic. T/F

F asymptomatic

Isolated IgA deficiency Because IgA is the major Ig in ________ , ______ are weakened, and infections occur in the ______,____, and ——- .

external secretions mucosal defenses respiratory, gastrointestinal, and urogenital tracts

Celiac dx is associated with ___ deficiency

IgA

IgA-deficient patients have a high frequency of respiratory tract allergy and a variety of autoimmune diseases, particularly _____ and ______

SLE and rheumatoid arthritis.

When transfused with blood containing normal IgA, some of these isolated IgA deficient patients develop _____________ reactions, because ________

severe, even fatal, anaphylactic the IgA behaves like a foreign antigen (since the patients do not produce it and are not tolerant to it)

Hyper-IgM Syndrome affected patients make ___ antibodies but are deficient in their ability to produce ________ antibodies

IgM; IgG, IgA, and IgE

Approximately 70% of individuals with hyper-IgM syndrome have the _____ form of the disease, caused by mutations in the gene encoding ______ located on Xq26. Or ___________.

X-linked CD40L CD40 receptor

Hyper-IgM Syndrome Remember that Bcells can be activated to plasma cells in 2 ways- 1)_______ on the surface of naïve Bcells to ___________ 2)_____ Antigen and presenting through ______ to T helper cells with _____ as 2nd stimulus. Activated CD4+ produce _____ and ____ which cause heavy chain class switch and production of Ig E, Ig G, Ig A

IgM receptors; IgM producing plasma cells Internalising; MHC class II; CD40 IL4 and IL5

Hyper IgM syndrome In the remaining persons the disease is inherited in an autosomal recessive pattern. Most of these patients have mutations in the gene encoding _____ or the enzyme called ________

CD40 activation-induced deaminase

Hyper IgM syndrome The serum of persons with this syndrome contains ________ levels of IgM but ______ IgA or IgE and ______ levels of IgG. The number of B and T cells is ______.

normal or elevated no; extremely low normal

In hyper IgM syndrome Many of the IgM antibodies react with elements of blood, giving rise to _______,_______, and _______. In older patients there may be uncontrolled proliferation of IgM-producing plasma cells with infiltrations of the _____ tract.

autoimmune hemolytic anemia, thrombocytopenia, and neutropenia gastrointestinal

DiGeorge Syndrome (Thymic Hypoplasia) T-cell deficiency that results from failure of ___________________ Due to __q__ —————

development of the third and fourth pharyngeal pouches. 22q11; microdeletion

DiGeorge Syndrome Thus, individuals with this syndrome have a variable loss of T cell–mediated immunity (resulting from ___________), tetany (resulting from lack of the _______ ), and congenital defects of the __________. In addition, the appearance of the _________ may be abnormal

hypoplasia or lack of the thymus parathyroids heart and great vessels mouth, ears, and facies

DiGeorge syndrome is a familial disorder. T/F

F not

DiGeorge syndrome It results from the ____ of a gene that maps to chromosome ___ Absence of _______ immunity is caused by low numbers of T lymphocytes in the blood and lymphoid tissues and poor defense against certain _____ and ______ infections.

deletion; 22q11 cell-mediated fungal and viral

In Digeorge syndrome The T-cell zones of lymphoid organs—_______ areas of the lymph nodes and the ____________ of the spleen—are depleted. Ig levels may be __________, depending on the _________________

paracortical; periarteriolar sheaths normal or reduced; severity of the T-cell deficiency.

Severe Combined Immunodeficiency (SCID) a constellation of genetically distinct syndromes, all having in common defects in ____________________________ immune responses

both humoral and cell-mediated

Often, the SCID defect resides in the ___-cell compartment, with a secondary impairment of ______ immunity

T humoral

SCID ETIOLOGY: Mainly 3- ________ (__) defect ____________ deficiency __________ deficiency

Cytokine receptor(IL2) Adenosine deaminase MHC class II

SCID The most common form, accounting for 50% to 60% of cases, is ______ The remaining cases of SCID are inherited as ___________

X-linked autosomal recessive.

SCID The genetic defect in the X-linked form is a mutation in the ________ subunit of cytokine receptors The most common cause of autosomal recessive SCID is a ____________________

common γ-chain (γc) deficiency of the enzyme adenosine deaminase (ADA)

The histologic findings in SCID depend on the underlying defect. In the two most common forms (ADA deficiency and γc mutation), the thymus is ____ and _______

small devoid of lymphoid cells.

In SCID caused by ADA deficiency, ___________ can be found, whereas in X-linked SCID the thymus contains lobules of ___________ cells resembling ___________ In either case other lymphoid tissues are hypoplastic as well, with marked depletion of ___-cell areas and in some cases both __-cell and __-cell zones.

remnants of Hassall's corpuscles undifferentiated epithelial ; fetal thymus. T T; B

TREATMENT of SCID •______ baby (_____) •____transplant (HSC- B & T cells) •Currently, ________ transplantation is the mainstay of treatment

Bubble; sterile isolation Stem cell bone marrow

_________ is the first human disease in which gene therapy has been successful

X-linked SCID

Wiskott-Aldrich Syndrome an X-linked recessive disease characterized by _______,_____,_______, and ______ a marked vulnerability to ______, ending in early death.

thrombocytopenia, petechial haemorrhage, eczema, and skin rashes recurrent infection

The Wiskott-Aldrich syndrome is caused by mutations in the gene encoding ________, which is located at Xp_____. This protein belongs to a family of proteins that are believed to link ________, such as antigen receptors, to ______ elements

Wiskott- Aldrich syndrome protein (WASP) 11.23 membrane receptors cytoskeletal

In WAS The thymus is morphologically Abnormal from the start T/F

F Normal at least early in the course of the disease,

In WAS Patients do not ___________, and the __________ is poor.

make antibodies to polysaccharide antigens response to protein antigens

In WAS IgM- ___ IgG- ______ IgE- _____ IgA- ____

low normal high high

In WAS, Patients are also prone to developing Hodgkin B-cell lymphomas T/F

F non- Hodgkin B-cell lymphomas

Genetic Deficiencies of the Complement System A deficiency of ____ is the most common of all.

Genetic Deficiencies of the Complement System In c2 deficiency, there is high susceptibility to infections

F there is little or no increase in susceptibility to infections,

Genetic Deficiencies of the Complement System In C2 deficiency, the dominant manifestation is an increased incidence of an _________ disease Why??

SLE-like autoimmune presumably, the alternative complement pathway is adequate for the control of most infections

Complement system deficiency Deficiency of components of the alternative pathway (______ and _____ ) is rare.

properdin and factor D

Complement system deficiency Deficiency of components of the alternative pathway It is associated with recurrent pyogenic infections The ___ component of complement is required for both the classical and alternative pathways a deficiency of this protein results in _____________

C3; susceptibility to serious and recurrent pyogenic infections.

Complement system deficiency C3 deficiency There is ___eased incidence of immune complex–mediated glomerulonephritis; in the absence of complement

incr

The terminal components of complement C5, 6, 7, 8, and 9 are required for the assembly of the membrane attack complex involved in the lysis of organisms. With a deficiency of these late-acting components, there is increased susceptibility to recurrent __________ infections;

neisserial (gonococcal and meningococcal)

Neisseria bacteria have (thin or thick ?) cell walls and are especially susceptible to the _________

Thin lytic actions of complement

A deficiency of C1 inhibitor gives rise to __________

hereditary angioedema

hereditary angioedema This autosomal (recessive or dominant?) disorder is (more or less?) common than complement deficiency states.

Dominant; more

The C1 inhibitor is a protease inhibitor whose target enzymes are ____ and ___ of the complement cascade, ______ of the coagulation pathway, and the _____ system

C1r and C1s factor XII; kallikrein

hereditary angioedema These patients have episodes of edema affecting skin ( _______ ) and mucosal surfaces such as the _____ and the _________ This may result in life-threatening asphyxia or nausea, vomiting, and diarrhea after minor trauma or emotional stress.

peri-orbital larynx gastrointestinal tract.

Acute attacks of hereditary angioedema can be treated with ________ prepared from ______

C1 inhibitor concentrates human plasma.

Deficiency of _________ is the cause of paroxysmal nocturnal hemoglobinuria.

other complement-regulatory proteins

paroxysmal nocturnal hemoglobinuria. In this disease there are mutations in enzymes required for _______ linkages, which are essential for the assembly of _______ and _______, both of which regulate complement.

glycophosphatidyl inositol decay-accelerating factor and CD59

Uncontrolled complement activation on the surface of red cells is believed to be the basis of _______ .

hemolysis

Mutations in the complement regulatory protein factor ___ underlie about 10% of cases of a renal disease called _______________ syndrome, which is characterized by _______ in the kidneys

H hemolytic uremic microvascular thrombosis

Presentation of Digeorge syndrome CATCH-22:

Cardiac defects Abnormal facies Thymic hypoplasia Cleft palate, Hypocalcemia

In SCID Recurrent viral, bacterial, fungal, and protozoal infections e.g ___,____,_____,____,_____ and a whole host of _____.

Candida albicans, P. jiroveci, Pseudomonas, cytomegalovirus, varicella, bacteria

FINDINGS in SCID •____________ (TRECs)  Part of newborn screening for SCID •Absence of _____ (CXR), _______ (lymph node biopsy), and T cells (flow cytometry)

T-cell receptor excision circles thymic shadow; germinal centers

PRESENTATION of Wiskott-Aldrich WAITER:

Wiskott-Aldrich: Immunodeficiency Thrombocytopenia, Eczema, Recurrent (pyogenic) infections

The three major routes of transmission are: _____ transmission: ______ transmission: ________ transmission

Sexual Parenteral Perinatal

The probability of HIV-1 transmission is highest for •_______(>___), •followed by _____ transmission (about __) •intermediate for _____ (about ___), and •lowest for ______ transmission (about ____).

blood transfusion ; 0.95 mother to- child ; 0.1 needle-sharing; 0.01 woman-to-man sexual ; 0.001

____ transmission: It is the main route of infection in more than ___% of cases of HIV.

Sexual 75

Viral transmission can occur in two ways: –__________ , and — By ___________

Direct inoculation of virus or infected cells into the blood vessels at the site of breach caused by trauma uptake into the mucosal dendritic cells (DCs).

Parenteral transmission: Three groups of individuals are at risk._________  ________  ____________

Intravenous drug abusers Hemophiliacs Transfusion of blood or blood components

HIV Because of recently infected individual may be antibody- ______ ( ______ ), there is a small risk of acquiring AIDS through transfusion of blood.

negative; seronegative

Organs from HIV-infected donors can also transmit AIDS. T/F

Perinatal transmission  Transmission of infection can occur by three routes:–_____ –______ –_______

In utero Perinatal spread After birth

Major mode of transmission of AIDS in children is by ????

Perinatal transmission

HIV occurs in two genetically different but related main forms, _____ and ___

HIV-1 and HIV-2.

HIV-1 is most common in the ____,____,______ HIV-2 is common in _______ and ____

United States, Europe, and Central Africa, West Africa and India.

HIV 1 is oncogenic T/F

Viral core of HIV It contains 1. Major capsid protein ___ 2. Nucleocapsid protein ____ 3. Two identical copies of single stranded RNA genome.4. Three viral enzymes: 1)____, 2) _______ and 3) ______.

p24 p7/p9. protease reverse transcriptase integrase

______ and the antibodies against it are used for the diagnosis of HIV infection in enzyme-linked immunosorbent assay (ELISA).

Major capsid protein

Lipid envelope of HIV The virus contains a lipoprotein envelope, which consist of lipid derived from the host cell and two viral glycoproteins. These glycoproteins are: 1)______ which project as a knob-like spikes on the surface and 2)_____ anchoring transmembrane pedicle. These glycoproteins are essential for HIV infection of cells.

gp120 gp41

HIV Genome It contains two main groups of genes and their products act as antigens. 1. Standard genes: HIV-1 RNA genome contains three standard retroviral genes, which are typical of retroviruses. These include:___,____, and _____ genes. Initially, the protein products of the gag and pol genes are translated into large precursor proteins and are later cleaved by the viral enzyme _____ to form mature proteins. 2. Accessory genes: HIV contains accessory genes: e.g.__,___ vif, nef, and vpr, and vpu. They regulate the synthesis and assembly of infectious viral particles and the pathogenicity of the virus.

gag, pol, and env; protease tat, rev,

HIV-1 enters cells through interaction with the ____ receptor and a chemokine co-receptor (____ or ___). The virus infects _____ cells and ____ expressing these receptors.

CD4; CXCR4 or CCR5 CD4-positive T; macrophages

HIV-1 can also infect dendritic cells. T/F

HIV-1 can be assigned to one of three classes based on its ability to use the two co-receptors. •Class __ :previously called ______ or __-tropic viruses. •Class __ - previously called ______ or __-tropic viruses. •Class _____ or ___ viruses.

R5: nonsyncytia - inducing (NSI) ; M X4; syncytiainducing (SI); T R5X4; dual

CD4-positive T cells in lymphoid tissues can express only CCR5 receptors T/F

F both CCR5 and CXCR4, and are the main target for replication in vivo.

Most individuals have the (R5 or X4?) virus at the time of diagnosis, whereas the presence of the (R5 or X4?) and __ virus is associated with progression to AIDS.

R5 X4; dual

Early acute phase of HIV: IT depends on blood CD4+ T-cell count. This divides the patients into three categories with counts being: •________ cells/μL •________ cells/μL •__________ /μL = full blown AIDS

greater than 500 between 200 to 500 less than 200 cells

People with healthy immune system usually have _____ CD4 cells/uL of blood

>950

______: Detects antibodies against viral proteins AND It is the most sensitive and best screening test for the diagnosis of AIDS. ________: Most specific or the confirmatory test for HIV.

ELISA Western blot

List 4 aids defining neoplasms

Anal carcinoma cervical cancer Kaposi sarcoma Non Hodgkin Bcell lymphoma