Diseases of the Immune System

These flashcards encompass the key concepts, definitions, and mechanisms related to the immune system and its diseases, facilitating focused study and review.

What is immunity?

Protection against infections.

What is the immune system?

A collection of cells and molecules responsible for defending the body against pathogens.

What causes immunodeficiency diseases?

Caused by defects in the immune system.

What are hypersensitivity disorders?

Diseases and tissue injury caused by the immune system.

What is the first line of defense in the innate immune system?

Innate immunity, mediated by cells and proteins that are always present and immediately active.

How long does it take for adaptive immunity to become activated?

Takes 3-7 days to become active.

What are the two types of adaptive immunity?

Humoral immunity and cell-mediated immunity.

Where do B cells mature?

In the bone marrow.

Where do T cells mature?

In the thymus.

What do CD4+ T helper cells do?

Secrete cytokines that help B cells produce antibodies and assist macrophages in destroying phagocytosed microbes.

What role do natural killer cells have in innate immunity?

Regulate immune response and secrete cytokines to activate macrophages.

What activates B cells in T cell-dependent responses?

Help from CD4+ T cells, which secrete cytokines and engage CD40 on B cells.

What are cytokines?

Secreted proteins that mediate immune and inflammatory reactions.

What triggers anaphylaxis in allergic reactions?

Re-exposure to a previously sensitizing allergen that binds to IgE on mast cells.

What is systemic lupus erythematosus characterized by?

Autoantibodies, especially antinuclear antibodies, leading to multi-organ damage.

What does amyloidosis result from?

Abnormal folding of proteins which aggregate and deposit as fibrils in extracellular tissue.

What is primary amyloidosis associated with?

Caused by clonal proliferation of plasma cells that synthesize abnormal Ig molecules.

How are Type II hypersensitivity reactions mediated?

By antibodies directed against target antigens on cell surfaces.

What are the hallmarks of chronic graft rejection?

Interstitial fibrosis and graft arteriosclerosis leading to progressive deterioration.

What is the main target of HIV infection?

CD4+ T cells.

What are the sub-types of T cells that constitute cell-mediated immunity?

CD8+ cytotoxic T lymphocytes and CD4+ helper T lymphocytes.

What is the primary role of dendritic cells in the innate immune system?

They are the most important antigen-presenting cells (APCs) for initiating T cell responses by capturing antigens and presenting them to T cells.

How do natural killer (NK) cells recognize and regulate immune responses?

They are regulated by inhibitory receptors that recognize self class I MHC on healthy cells and activating receptors that recognize stressed or infected cells.

What are Pattern Recognition Receptors (PRRs)?

Receptors that recognize components of pathogens (pathogen-associated molecular patterns - PAMPs) or damaged cells (damage-associated molecular patterns - DAMPs).

What are the distinct types of receptors that recognize extracellular patterns?

Toll-like receptors (TLRs) and C-type lectin receptors.

What are the distinct types of receptors that recognize intracellular patterns?

NOD-like receptors and RIG-like receptors.

In adaptive immunity, what must happen for T lymphocytes to recognize an antigen?

Antigen must be displayed by MHC molecules; T cells cannot recognize free antigen.

What is the function of Naïve CD4+ T cells?

They differentiate into helper T cells, produce cytokines, and stimulate B cells and macrophages, recognizing class II MHC.

What is the function of Naïve CD8+ T cells?

They develop into cytotoxic T cells (CTL) that kill infected cells and tumor cells, recognizing class I MHC.

What is the role of the T cell receptor (TCR)?

It recognizes peptide antigens presented by MHC molecules, providing the first signal for T cell activation.

Which antibody isotypes are expressed on B cells?

IgD and IgM antibodies.

What are the main functions of IgA antibodies?

They are the major type found in mucosal secretions, providing protection at epithelial surfaces.

What is the function of IgE antibodies in the immune response?

They attach to mast cells, are important for hypersensitivity reactions (allergies), and protect against helminth infections.

What is the most prevalent antibody in the blood and its function?

IgG, which is important for opsonization, complement activation, and passive immunity (crossing the placenta).

Which cells express Class I MHC molecules and what T cells recognize them?

Expressed on all nucleated cells (HLA-A, HLA-B, HLA-C), recognized by CD8+ T cells.

Which cells express Class II MHC molecules and what T cells recognize them?

Expressed by dendritic cells, macrophages, and B cells (HLA-DP, HLA-DQ, HLA-DR), recognized by CD4+ T cells.

What is the importance of HLA genes being highly polymorphic?

There are thousands of MHC variants in the human population, leading to different HLA alleles in unrelated individuals, which is important for transplantation.

Where do naïve B and T cells mature?

In primary/central/generative lymphoid tissues: the bone marrow (for B cells) and the thymus (for T cells).

What is the function of lymph nodes in the immune system?

They bring antigens, APCs, and lymphocytes together, allowing APCs to sample antigen and dendritic cells to present antigens to T cells.

What are some examples of innate immune cytokines?

TNF, IL-1, IL-12, type I IFNs, type II IFN (IFN-\gamma), and chemokines.

What are some examples of adaptive immune cytokines?

IL-2, IL-4, IL-5, IL-17, and IFN-\gamma.

What are the two signals required for T cell activation?

Signal 1: Recognition of antigen by the T cell receptor (TCR). Signal 2: A costimulatory signal, such as CD28 on T cells binding to B7 proteins (CD80 and CD86) on APCs.

What is the role of coinhibitory receptors like CTLA-4 and PD-1?

They block B7 molecules and inhibit TCR and CD28 signals, preventing T cell activation and helping to maintain tolerance.

What are the primary functions of Th1 cells?

They activate macrophages via the secretion of IFN-\gamma.

What are the primary functions of Th2 cells?

They produce IL-4 to stimulate B cells to differentiate into IgE-secreting plasma cells, IL-5 to activate eosinophils, and IL-13 to activate mucus secretion.

What is the mechanism by which CD8+ cytotoxic T cells (CTL) kill infected cells?

CTLs release perforin, which enables granzyme to enter the target cell, activating caspases and inducing apoptosis.

What is the difference between T cell-dependent and T cell-independent B cell activation?

T cell-dependent activation requires help from CD4+ T cells, while T cell-independent activation can be directly triggered by polysaccharide and lipid antigens linking antibodies on B cells.

How do antibodies combat microbes through neutralization?

Antibodies coat the microbe and block its ability to infect cells.

How do antibodies contribute to opsonization and phagocytosis?

IgG coating on microbes acts as an "eat me" signal for phagocytes.

What are the three main causes of hypersensitivity reactions?

Autoimmunity, excessive or inappropriate reactions against microbes, and reactions against environmental antigens.

What is the sequence of events in the initial activation phase of Type I hypersensitivity (allergy)?

First exposure to an allergen activates CD4+ T cells, which differentiate into Th2 cells. Th2 cells secrete IL-4 and IL-13 (stimulating IgE production) and IL-5 (activating eosinophils).

What mediators are released by mast cells upon re-exposure to an allergen in Type I hypersensitivity?

Vasoactive amines (e.g., histamine), neutral proteases (e.g., tryptase), lipid mediators (e.g., prostaglandins, leukotrienes), and cytokines (e.g., TNF, chemokines).

What are some clinical examples of Type II hypersensitivity where antibodies interfere with normal cell function?

Pernicious anemia and Graves disease (antibodies against essential proteins) and Myasthenia gravis (antibodies against acetylcholine receptors).

What is the immunological mechanism of Type III hypersensitivity reactions?

Antigen-antibody complexes (immune complexes) form in circulation and deposit in blood vessels, leading to complement activation and inflammation.

In which tissues do immune complexes tend to deposit in Type III hypersensitivity?

Kidney glomeruli (leading to glomerulonephritis), joints (arthritis), and small blood vessels (vasculitis).

What are the two main forms of T cell mediated (Type IV) hypersensitivity?

Cytokine-mediated inflammation (e.g., delayed-type hypersensitivity like the tuberculin reaction) and direct cell cytotoxicity (e.g., CTLs against organ transplants).

What is central tolerance in the context of autoimmunity?

The elimination or inactivation of self-reactive lymphocytes during their development in the thymus (T cells) and bone marrow (B cells) through negative selection or receptor editing.

What is the role of AIRE protein in central tolerance?

AIRE (Autoimmune Regulator) protein presents self-antigens to the thymus to test for self-reactive immature T lymphocytes, leading to their deletion if they react strongly.

What is peripheral tolerance, and how do regulatory T cells (Tregs) contribute to it?

The elimination or inactivation of self-reactive lymphocytes in peripheral tissues. Tregs express FoxP3 and CTLA-4, inhibiting T cell activation, and secrete anti-inflammatory cytokines like IL-10 and TGF-\beta.

How can microbial infections contribute to the breakdown of T cell tolerance, leading to autoimmunity?

Microbes can stimulate the expression of costimulatory molecules on APCs and production of cytokines, which activate T cells and can extend responses to self-tissues via molecular mimicry.

What are the characteristics of Sjögren syndrome?

Characterized by dry eyes (keratoconjunctivitis sicca) and dry mouth (xerostomia) due to immune-mediated damage to salivary and lacrimal glands.

What characterizes systemic sclerosis (scleroderma)?

Excessive fibrosis in multiple tissues, obliterative vascular disease, and production of autoantibodies like ANAs, typically starting with cutaneous fibrosis.

What is graft rejection in transplantation immunology?

A process where recipient T cells and antibodies specific for graft antigens react with and destroy the transplanted tissue.

What mediates hyperacute graft rejection?

Preformed antibodies in the recipient that are specific for antigens on graft endothelial cells, leading to immediate endothelial injury and thrombosis.

What are the two main forms of acute graft rejection?

Acute cellular rejection (mediated by T cells) and acute antibody-mediated (vascular or humoral) rejection (mediated by antibodies binding vascular endothelium).

What is the consequence of immunosuppression required for organ transplantation?

Increased susceptibility to infection, reactivation of latent viruses, and an increased risk of oncovirus-induced tumor formation.

What is Graft-versus-Host Disease (GVHD)?

A complication of hematopoietic stem cell transplantation where immunologically competent donor T cells recognize recipient alloantigens and attack the recipient's tissues.

What are primary (congenital) immunodeficiencies?

Inherited genetic disorders that impair immunity, usually presenting in infants or young children with recurrent infections.

What is Severe Combined Immunodeficiency (SCID)?

A group of syndromes characterized by impaired development of mature T and/or B cells, leading to severe recurrent infections and often oral candidiasis and persistent diaper rash in infants.

What is X-linked agammaglobulinemia (Bruton disease) characterized by?

Failure of pre-B cells to differentiate into mature B cells due to mutations in Bruton tyrosine kinase (BTK), resulting in an absence of antibodies in the blood and recurrent respiratory infections after 6 months of age.

What is DiGeorge Syndrome (thymic hypoplasia)?

A congenital defect in thymic development, leading to deficient T cell maturation and recurrent infections in infants.

What is Hyper IgM syndrome characterized by?

Normal or high levels of IgM but decreased IgG, IgA, and IgE due to an inability of T cells to activate B cells and macrophages, often caused by mutations in the CD40L gene on T cells.

What is Common Variable Immunodeficiency (CVID)?

A group of disorders with hypogammaglobulinemia, normal numbers of B cells but no plasma cells, typically presenting with recurrent sinopulmonary infections in childhood or adolescence.

What is Isolated IgA Deficiency?

The most common primary immune deficiency disease, characterized by a block in the terminal differentiation of IgA-secreting B cells, often asymptomatic or resulting in sinopulmonary and intestinal infections.

What is Chronic Granulomatous Disease?

A primary innate immunodeficiency caused by a defect in genes encoding phagocyte oxidase, leading to defective bacterial killing and increased susceptibility to recurrent bacterial infections.

What is the main target cell for HIV infection?

CD4+ T cells, which are infected via the CD4 receptor and chemokine coreceptors CCR5 and CXCR4.

What viral enzymes are essential for the HIV life cycle?

Reverse transcriptase, integrase, and protease.

What is the initial phase of HIV infection called, and what are its characteristics?

The acute phase, where HIV enters mucosal surfaces, infects and kills memory CD4+ T cells, leading to a self-limited flu-like illness (acute HIV syndrome).

What defines the AIDS stage of HIV infection?

A breakdown of host defense, dramatic increase in viremia, and life-threatening clinical diseases characterized by opportunistic infections and secondary neoplasms.

What are some common opportunistic infections seen in AIDS patients?

Pneumonia due to Pneumocystis jirovecii, candidiasis, cytomegalovirus, Mycobacterial infections, cryptococcosis, and Toxoplasma gondii.

What type of protein structure is characteristic of amyloid deposits?

Abnormally folded proteins that assume a \beta-pleated sheet conformation.

What are the three most common forms of amyloid proteins?

Amyloid light chain (AL), Amyloid-associated (AA), and \beta-amyloid protein (A\beta).

What is primary amyloidosis associated with and what is its protein type?

Associated with clonal plasma cell proliferation (e.g., in multiple myeloma) and is typically of the AL type.

What is secondary amyloidosis associated with and what is its protein type?

Associated with underlying chronic inflammatory processes (e.g., rheumatoid arthritis, inflammatory bowel disease) and is typically of the AA type.

Which of the following is an innate immune cell?

Dendritic Cell

Graves disease is an example of which type of hypersensitivity reaction?

Type II (Antibody mediated)

Cell mediated immunity is mediated by which cell type?

T lymphocytes

Which T cell receptor recognizes costimulators?

CD28

Class II MHC is expressed on which of the following:

Dendritic cells

Circulating immune complexes developed in the circulation and being deposited in the vessels walls is characteristic of which of the following type of hypersensitivity?

Type III (Immune complex-mediated)

Hyper-IgM Syndrome is associated with

Normal levels of IgM but decreased IgG, IgA, and IgE due to inability of T cells to activate B cells

Indirect recognition of allografts occurs when

Recipient antigen presenting cells present antigen to recipient T cells

Which disease is associated with high serum \beta2-macroglobulin deposition in joints and muscle after not being filtered out with dialysis?

Hemodialysis associated amyloidosis

Which disease is associated with autoantibodies against DNA topoisomerase I and anticentromere antibody?

Systemic sclerosis