6 - Diseases of the Immune System Flashcards
Describe the components of the innate immune system.
Epithelial barriers that block entry of microbes, phagocytic cells (mainly neutrophils and macrophages), dendritic cells, natural killer (NK) cells, and several plasma proteins, including the proteins of the complement system
What are pathogen-associated molecular patterns? What type of immunity is preprogrammed to react to them?
Certain microbial components that are shared among related microbes and are often essential for infectivity; innate immunity
What innate cellular receptors recognize pathogen-associated and damage-associated molecular patterns?
Pattern recognition receptors (of which, Toll-like, C-like leptin, and NOD-like receptors are a type)
What are two modes of innate reactivity?
Inflammation and antiviral defense
What makes up the adaptive immune system?
Lymphocytes and their products
What are the three main types of T lymphocyte and what do they do?
Helper T lymphocytes stimulate B lymphocytes to make antibodies and activate other leukocytes (e.g., phagocytes) to destroy microbes; cytotoxic T lymphocytes (CTLs) kill infected cells; and regulatory T lymphocytes limit immune responses and prevent reactions against self-antigens.
What does the T Cell Receptor (TCR) sense?
Peptide antigens that are presented by major histocompatibility complex (MHC) molecules on the surfaces of antigen-presenting cells
What two components form the TCR complex?
The TCR and CD3
What is the most important antigen-presenting cell for initiating T-cell responses against protein antigens?
Dendritic cells
What are the generative lymphoid organs?
The thymus and bone marrow
What are the peripheral lymphoid organs? What is their purpose?
Lymph nodes, spleen, and the mucosal and cutaneous lymphoid tissues;
concentrate antigens and immune cells in a way that optimizes interactions among these cells and the development of adaptive immune responses
What is the germinal center of a lymph node?
A central region of some follicles
What are human MHCs called?
Human leukocyte antigens
What is the function of MHC molecules?
To display peptide fragments of protein antigens for recognition by antigen-specific T cells
Are MHC I molecules expressed on platelets?
Yes
What do MHC I molecules display?
Peptides that are derived from proteins, such as viral and tumor antigens, that are located in the cytoplasm and usually produced in the cell, and class I–associated peptides are recognized by CD8+ T lymphocytes
Which HLAs code for MHC I molecules?
HLA A, B, and C
Which HLAs code for MHC II molecules?
HLA D (DR, DP, DQ)
Where do MHC II molecules display?
Antigens that are internalized into vesicles, and are typically derived from extracellular microbes and soluble proteins.
How do adjuvants help to increase immune response to vaccines?
They are microbial mimics
What are the components of a type I hypersensitivity reaction?
The injury is caused by TH2 cells, IgE antibodies, and mast cells and other leukocytes. Mast cells release mediators that act on vessels and smooth muscle and proinflammatory cytokines that recruit inflammatory cells.
Describe type II hypersensitivity reactions.
Secreted IgG and IgM antibodies injure cells by promoting their phagocytosis or lysis and injure tissues by inducing inflammation
Describe a type III hypersensitivity reaction.
IgG and IgM antibodies bind antigens usually in the circulation, and the antigen-antibody complexes deposit in tissues and induce inflammation
Describe the components of a type IV hypersensitivity reaction.
Sensitized T lymphocytes (TH1 and TH17 cells and CTLs) are the cause of the tissue injury
What type of hypersensitivity reactions are allergies?
Type I
What is the Arthus reaction (local immune complex disease)?
A localized area of tissue necrosis resulting from acute immune complex vasculitis, usually elicited in the skin after injection with an antigen
What is self-tolerance?
A lack of responsiveness to an individual’s own antigens
What is immunologic tolerance?
The phenomenon of unresponsiveness to an antigen induced by exposure of lymphocytes to that antigen
What is central immunologic tolerance?
Self-reactive T and B cells are killed or rendered harmless
How does immunologic tolerance occur in the periphery?
Anergy, suppression, and deletion
What set of genes makes the greatest contribution to autoimmunity?
HLA alleles
What is an example of autoimmunity triggered by infections?
Molecular mimicry (Rheumatic heart disease, Guillan-Barr)
Are autoimmune diseases usually chronic and progressive?
Yes.
What are four types of antigens targeted by antinuclear antibodies in SLE?
DNA, histones, other nuclear proteins, nucleolar antigens;
antibodies to double-stranded DNA and the so-called Smith (Sm) antigen are virtually diagnostic of SLE.
What disease is characterized by dry eyes, dry mouth, and arthritis due to infiltration of the lacrimal and salivary glands and subsequent fibrosis?
Sjogren’s syndrome
Describe systemic sclerosis (scleroderma).
(1) chronic inflammation thought to be the result of autoimmunity,
(2) widespread damage to small blood vessels
(3) progressive interstitial and perivascular fibrosis in the skin and multiple organs
What are the three pathologies of systemic sclerosis?
Autoimmune responses, vascular damage, and collagen deposition
What organ systems are affected by systemic sclerosis?
Skin, alimentary tract, musculoskeletal system, kidneys, lungs, and heart
What is mixed connective tissue disease?
A disease with clinical features that are a mixture of the features of SLE, systemic sclerosis, and polymyositis
What is polyarteritis nodosa?
Necrotizing inflammation of the walls of blood vessels
What is the T Cell-mediated transplant rejection?
Acute cellular reaction and chronic cellular reaction
What are the main antibody-mediated transplant rejections?
Hyperacute rejection, acute antibody-mediated rejection, and chronic antibody-mediated rejection
What is a possible infectious consequence of transplant-related immunosuppression?
Reactivation of polyomavirus in the lower genitourinary tract
(also increased risk of EBV-induced lymphoma, HPV-induced squamous cell carcinoma, and Kaposi sarcoma)
What is graft-versus-host disease (GVHD)?
GVHD occurs when immunologically competent cells or their precursors are transplanted into immunologically crippled recipients, and the transferred cells recognize alloantigens in the host and attack host tissues
GVHD is seen most commonly among recipients of what type of transplant?
Hematopoietic stem cell transplants
What is a frequent complication of hematopoeitic stem cell transplants?
Immunodeficiency
What is another term for a transplant?
An allograft
What is the telltale sign of primary immunodeficiencies?
Recurrent infections in infants aged 6 months to 2 years
What are some examples of primary immunodeficiencies?
SCID, defects in leukocyte adhesion, phagolysosome function, microbicidal activity, TLR signaling, complement (C2 or C4)
What is X-linked SCID?
A mutation in the common γ-chain (γc) subunit of cytokine receptors
What is autosomal recessive SCID?
A deficiency of adenosine deaminase
What is X-Linked Agammaglobulinemia?
X-linked agammaglobulinemia is characterized by the failure of B-cell precursors (pro-B cells and pre-B cells) to develop into mature B cells
The disease usually does not become apparent until about 6 months of age, as maternal immunoglobulins are depleted)
What is hyper-IgM syndrome?
In this disorder, the affected patients make IgM antibodies but are deficient in their ability to produce IgG, IgA, and IgE antibodies.
What is Wiskott-Aldrich syndrome?
An X-linked disease characterized by thrombocytopenia, eczema, and a marked vulnerability to recurrent infection, resulting in early death
What are some causes of secondary immunodeficiencies?
HIV, chemotherapy or irritation, cancer involvement in the bone marrow, malnutrition, diabetes, chronic infection, spleen removal
Who is the largest group affected by HIV?
Homosexual or bisexual men (more than 50% of reported cases)
What demographic groups are at greatest risk for HIV transmission?
Homosexual or bisexual men, intravenous drug users, hemophiliacs, recipients of blood transfusions, poor and minority women, HIV infection of the newborn
What are the three major routes of HIV transmission?
Sexual contact (75%), parenteral inoculation (IV drug users, hemophiliacs, other blood transfusions), passage from mother to child
How can mothers pass HIV on to their children?
(1) transplacental transmission; (2) during delivery; (3) through breast milk
What are the properties of HIV?
A nontransforming human retrovirus (family lentivirus)
What is HIV’s structure?
(1) The major capsid protein p24; (2) nucleocapsid protein p7/p9; (3) two copies of viral genomic RNA; and (4) the three viral enzymes (protease, reverse transcriptase, and integrase)
What RNA genes does the HIV-1 contain?
gag, pol, env
What are the two major targets of HIV?
The immune system and the CNS
What are the two principal HIV glycoproteins that help it to bind the CD4 molecules?
gp41 and gp120
What happens once the RNA genome of the virus has been endocytosed?
The virus undergoes reverse transcriptase, leading to the formation of cDNA for integration into the host genome
Is HIV able to efficiently infect naive (unactivated) T cells?
No. In most cases, the activation of the infected CD4+ T cell results in cell lysis
Does HIV infect memory or activated T cells?
Both.
Are only CD4+ cells infected by HIV?
No, also macrophages and dendritic cells
Where are potential reservoirs of HIV?
Dendritic cells in follicular germinal cells
How does HIV cross the blood-brain barrier?
Via infected monocytes
What are the stages of HIV infection?
(1) An acute retroviral syndrome, (2) a middle, chronic phase (usually asymptomatic), (3) clinical AIDS
Describe the acute (early) stage of HIV infection.
Acute (early) infection is characterized by infection of memory CD4+ T cells (which express CCR5) in mucosal lymphoid tissues, and death of many infected cells.
Mucosal infection is followed by dissemination of the virus and the development of host immune responses. Sore throat, myalgias, fever, weight loss, and fatigue, resembling a flulike syndrome.
Describe the chronic (second) stage of HIV infection (clinical latency period).
Lymph nodes and the spleen are sites of continuous HIV replication and cell destruction; during this period of the disease, few or no clinical manifestations of the HIV infection are present.
What are some possible signs or symptoms of patients with HIV in the clinical latency period?
If not asymptomatic, minor opportunistic infections such as oral candidiasis (thrush), vaginal candidiasis, herpes zoster, and perhaps mycobacterial tuberculosis
What are the signs and symptoms of the development of AIDS?
A breakdown of host defense, a dramatic increase in plasma virus, and severe, life-threatening clinical disease.
In the United States, the typical adult patient with AIDS presents with fever, weight loss, diarrhea, generalized lymphadenopathy, multiple opportunistic infections, neurologic disease, and, in many cases, secondary neoplasms.
What are the two main cllinical signs of AIDS development?
A dramatic increase in plasma virus and the onset of severe, life-threatening clinical disease
What accounts (generally) for the majority of deaths in untreated AIDS patients?
Opportunistic infections (various pneumonias, toxoplasmosis, candida, candidiasis, cytomegalovirus, etc,)
Worldwide, what accounts for 33% of AIDS patient deaths?
Tuberculosis
The incidence of what tumors is increased in AIDS patients? What oncogenic viruses are associated with each one?
Kaposi sarcoma (HHSV-8), B-cell lymphoma (EBV), cervical cancer in women (HPV), anal cancer (in men) (HPV)
What enzymes are targeted by antiretroviral drug therapy?
Viral reverse transcriptase, protease, integrase
What is amyloidosis?
A condition associated with a number of inherited and inflammatory disorders in which extracellular deposits of fibrillar proteins are responsible for tissue damage and functional compromise
What are some possible causes of amyloidosis?
The deposition of these proteins may result from: (1) excessive production of proteins that are prone to misfolding and aggregation; (2) mutations that produce proteins that cannot fold properly and tend to aggregate; (3) defective or incomplete proteolytic degradation of extracellular proteins.
With the progressive accumulation of amyloid, what can happen to adjacent cells?
The produce pressure and atrophy adjacent cells
What is amyloid? Why does it accumulate in amyloidosis?
A continuous, nonbranching protein fibrils;
amyloidosis results from abnormal folding of proteins, which become insoluble, aggregate, and deposit as fibrils in extracellular tissues
Does amyloidosis result in localized or systemic deposits of amyloid?
It can be either; organs can be uniquely deposited or it can be systemic
