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Unit 4
immune responses
113
Pathology
Undergraduate 3
12/09/2014

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Term
Where do lymphocytes come from?
Definition
stem cells in the bone barrow
Term
What are the two types of lymphocytes?
Definition
T cells
-thymus dependent

B Cells
-bursa (bone marrow)
Term
What are the central lymphoid tissues?
Definition
thymus & bone marrow
Term
What are the peripheral lymphoid tissues?
Definition
lymph nodes
spleen
tonsils
gut-associated lymphoid tissue
Term
Where is the thymus?
Definition
in the chest cavity
Term
True or False

The thymus develops as mammals age
Definition
false

it shrinks
Term
How can you differentiate T cells & B cells?
Definition
-presence of antigens using specific antibodies
Term
What characterizes B-cells?
Definition
presence of a B-cell antibody-receptor complex
Term
What happens when antibodies come in contact with antigens?
Definition
1. B cells proliferate (clonal expansion)
2. Differentiate into Plasma Cells & Memory Cells
Term
What are plasma cells? What is their appearance?
Definition
B cells which secrete antibody (immunoglobulin) specific to a particular antigen

-nucleus is off center, cartwheel chromatin pattern, obvious Golgi apparatus
Term
What are memory cells?
Definition
B cells which have a long lifespan, will provide a 'residual' population to invoke a rapid immune response if the antigen in question is encountered in the future
Term
How do T cells interact with antigens?
Definition
interacts with fragments of antigens expressed on the surface of cells that have digested a pathogen or are expressing an antigen abnormally
Term
What happens after T cells interact with antigens?
Definition
Proliferation (Clonal Expansion) & differentiation into CD4+ or CD8+
Term
What are CD4+ cells?
Definition
'helper' cells
-secrete cytokines which upregulate the immune response
Term
What are the different types of helper cells?
Definition
Th3-Cell Response
Th2-Cell Response
Term
What do Th3-Cells do?
Definition
-release Interferon-gamma IFN-Y
-activate macrophages & B cells
-trigger B cells to secrete antibodies
Term
What do Th2-Cells do?
Definition
Release interleukins to activate mast cells & eosinophils
Term
What does the 'CD' mean in CD-4 & CD-8 cells?
Definition
Cluster Designation
-antigens on the surface of T cellsm
Term
What is the 'normal' ration of CD4+ to CD8+ cells? How does this change in AIDS?
Definition
2:1

greatly reduced in patients with AIDS
Term
What are CD8+ cells?
Definition
cytotoxic T-cells which directly kill virus-infected cells/tumour cells

*lesser effect of cytokine release
Term
What are the 3 important functions of activated T cells in the immune system?
Definition
1. Cell-mediated immunity (killing recognized cells)
2. Helper roles (cytokines to help activate B ell synthesis of antibodies)
3. Delayed hypersensitivity
Term
What are natural killer cells?
Definition
-'innate immunity' cells which will kill cells which show signs of stress

-have inhibitory receptors to prevent activation & therefore prevent killing 'healthy' cells
Term
What do inhibitor receptors of killer cells recognize on healthy cells?
Definition
MHC self class I receptors on the healthy cells
Term
What roles do macrophages play in the early immune response?
Definition
-induce secretion of IL-1 which activates T cells
-antigen presentation by internalizing the antigen and expressing the Ag on the surface to activate T cells & release lymphokines
Term
What are the two major types of dendritic cells?
Definition
Interdigitating Dendritic Cells
Follicular Dendritic Cells
Term
What do Interdigitating Dendritic Cells do? (4 steps)
Definition
-capture antigens in tissues
-migrate to lympgoid
-present the antigen to lymphoid T-cells
-trigger cytokine secretion
Term
What do follicular dendritic cells do?
Definition
-capture complement proteins & Ab/Ag in lymphoid tissues
-present antigen to lymphoid B-cells
Term
What are the Antigen-Presenting cells?
Definition
Macrophages
IDC
FDC
Term
What are the 5 main classes of immunoglobulins & what are their key features?
Definition
IgG
-colostrum immunity, opsonize microbes

IgA
-in mucosal tissues (respiratory & GI)

IgE
-coats parasites

IgM
-bacteria & viruses

IgD
Term
What gives immunoglobulins their specifity?
Definition
the AA sequence of the 'light' chain
Term
Where do complement proteins bind to an immunoglobulin molecule?
Definition
the 'constant' regions of the light & heavy chains
Term
How long does it take for antibodies to appear in the serum after exposure to an antigen?
Definition
up to 2 weeks
Term
Why are Ig levels so low around 3-4 months of age?
Definition
maternally derived antibodies are decreasing yet the lymphoid tissue has not developed enough to produce its own antibodies
Term
What happens if non-specific defenses & non-specific immune response is not enough to stop antigens once they enter the body?
Definition
the antigens will enter the lymphatic system & travel to lymph nodes
Term
What happens to antigens when they reach the lymph nodes?
Definition
-processed by macrophages & presented to T & B cells
-activated T cells are produced
-plasma cells are produced (secrete antibody)
-antibody enters efferent lymphatic vessels & enters blood plasma
Term
What is a 'hyperplasic' lymph node?
Definition
a lymph node with antigens which has stimulated lots of activity
Term
What is agglutination? Why is it important?
Definition
formation of clumps of Ag & Ab complexes due to crosslinking between the complexes

-makes it easier for phagocytes to trap & consume immune complexes
-may neutralize toxic antigens
Term
What is opsonization
Definition
coating the antigen with antibody to increase phagocytosis by leukocytes
Term
What is the 'Fc' portion of an immunoglobulin for?
Definition
the portion that will be recognized by leukocytes with receptors specific to that antibody
Term
What is complement fixation?
Definition
-9 plasma proteins which react in sequence to form a cytotoxic complex which can lyse a cell membrane
Term
What are the effects of complement activation?
Definition
-complement fixation
-C3a/C5a = vasodilation & permeability, chemotactic
-C3b is an opsonin
Term
True or False

agglutination & opsonization occur only if the antigen is a macromolecule
Definition
false

only if the antigen is cellular
Term
What happens if the antigen is a macromolecule?
Definition
Ag-Ab complexes form, create a large macromolecular complex to make phagocytosis easier
Term
What are the characteristics of an immune response?
Definition
specificity
memory
amplification (enhanced response on second exposure to antigen)
Term
What is happening during the 'lag' period of a primary immune response? What Ig is produced first?
Definition
B cells are undergoing clonal expansion to produce lots of plasma cells which secrete the specific antibody

IgM first
Term
What immunoglobulin is produced mainly during the secondary immune response?
Definition
IgG
Term
What are some examples of passive immunity?
Definition
Transplacental (IgG across placenta in-utero)
Colostral (Ig through milk)
Therapeutic (administration eg. snake antivenins)
Term
True or False

Passive immunity has very long effects
Definition
false

it will be metabolized by the body, is short-acting
Term
What is an attenuated vaccine?
Definition
vaccine with an organism that has been rendered harmless
Term
The toxin/organism in a vaccine retains its _____ but not its ______
Definition
antigenicity but not its pathogenicity
Term
Why are vaccines administered in a series to young mammals?
Definition
-need to vaccinate when maternal antibodies e declining otherwise they will block the vaccine
-lots of variability in the time for this between individuals, so we give a series to allow for room for errow
Term
studying antigen-antibody reactions in a lab setting is known as....
Definition
serology
Term
What is a titer?
Definition
the dilution at which the reactivity between Ag & Ab is not affected
Term
True or False

A low titer indicates high antibody levels
Definition
false

high antibody levels
Term
What is hypersensitivity?
Definition
when an immune response is so reactive that it leads to tissue injury
Term
What are the 4 types of hypersensitivity reactions and how are they mediated?
Definition
Anaphylactic
Antibody-Dependent
Complex-mediated
Cell-mediated

Types I, II & III: mediated by antiobody reactions
Type IV: cell mediated responses
Term
What are the two types of Type I Sensitivity?
Definition
Localized or Systemic
Term
What would happen during the first exposure to an antigen in an individual with Type I Localized Hypersensitivity?
Definition
1. Allergen introduced
2. Th2 cells activated
3. IgE produced
4. Cytokine secretion
5. IgE binds to Fc receptors on mast cells
Term
What would happen during the second exposure to an antigen in an individual with Type I Localized Hypersensitivity?
Definition
1. Allergen activates mast cells tagged with the IgE
2. Mediators secreted which cause pathological manifestations of immediate hypersensitivity
Term
What happens during the late-phase reaction of Type I hypersensitivity?
Definition
-eosinophils, neutrophils & lymphocytes infiltrate tissue
-epithelial damage
-bronchospasm
Term
What is the initial response of Type I hypersensitivity? (3)
Definition
vasodilation
vascular leakage
smooth muscle spasm
Term
True or False

Anaphylaxis is associated with Type I Localized Hypersensitivity
Definition
False

SYSTEMIC
Term
What happens during secondary exposure to an allergen in Type I hypersensitivity, in regards to mast cells?
Definition
the IgE coating mast cells cross links with Fc triggering release of mediators
Term
What are the primary mediators released from mast cells?
Definition
-histamine, proteases, chemotactic factors
Term
What are secondary mediators?
Definition
Generated mediators produced by activation of Phospholipase A which targets arachidonic acid metbolism

-secrete cytokines, chemokines, prostaglandins etc.
Term
What are the 3 mechanisms that might cause Type II Hypersensitivity?
Definition
Opsonization & Phagocytosis
Inflammation
Antibody-Mediated Cellular Dysfunction
Term
Why might opsonization cause Type II hypersensitivity?
Definition
-cells coated with Ab are opsonized (more susceptible to phagocytosis
-body might mistake a normal cell surface component as being foreign & phagocytize it
Term
Why might inflammation cause Type II hypersensitivity?
Definition
-antibodies bound to antigens activate the complement system
-complement products recruit neutrophils & monocytes triggering inflammation
-products also opsonize cells & can lyse cells (especially RBCs)
Term
What Antibody-Mediated Cellular Dysfunction?
Definition
-antibodies can be formed against cell surface molecules/receptors to inhibit cell function without causing necrosis

e.g. Myaesthenia gravis = antibodies against Ach receptors = muscle weakness
Term
What is Type III hypersensitivity?
Definition
-an antigen elicits formation of an antibody
-the interaction between the Ag & Ab form complexes which are deposited in walls of small vessels
-this activates complement, acute inflam & tissue injury
Term
Why does Type II hypersensitivity cause tissue injury?
Definition
neutrophils are recruited to phagocytize the immune complexes which causes secretion of pro-inflammatory substances
Term
What is the end result of immune-complex mediated hypersensitivity?
Definition
-fibrinoid necrosis of small vessels
(necrotizing vasculitis)
Term
What happens if an immune-complex mediated hypersensitivity occurs in the renal glomerular vessels?
Definition
glomerular nephritis
Term
What is fibrinoid necrosis?
Definition
necrosis of collagen & smooth muscle, has a homogenous fibrin-like appearance
Term
What type of hypersensitivity is associated with hypersensitivity pneumonitis?
Definition
Localized Type III
Term
What are the two types of Type III hypersensitvity?
Definition
Localized & Systemic Immune Complex Disease
Term
What is Local Immune Complex Disease?
Definition
necrosis occurs at site of antigen antry
repeated exposure = lots of specific antibody in the serum
-future exposure will lead to Ag/Ab complexes deposited in small blood vessels leading to local tissue necrosis
Term
What is Systemic Immune Complex Disease?
Definition
-exposure to large dose of an antigen produces an antibody
-Ag/Ab complexes are formed in the blood
-if more Ag than Ab the complexes formed are soluble and can pass through pores & be deposited in vessel walls
-leads to vascular necrosis
Term
Why is an excess of Ab during the formation of Ag/Ab complexes not a significant concern?
Definition
cannot pass through endothelial pores as complexes are large, are removed by mononuclear phagocytes
Term
Where are immune complexes typically deposited?
Definition
in walls of vascular system, especially small vessels

also kidneys & joints
Term
What is Type IV Hypersensitivity?
Definition
-sensitized T cells are either directly cytotoxic or secrete cytokines which recruit effector cells that cause injury
Term
What cells characterize Delayed Type Hypersensitivity?
Definition
-CD4+ cells
-macrophages
Term
What happens when a sensitive person undergoes exposure poison ivy?
Definition
1. Naive CD4 cells recognize antigens, create memory CD4 cells, Th1 effectors
2. Subsequent exposure triggers cytokine excretion
3. IFN-Y activates macrophages which produce tissue-damaging substances & promote fibrosis & inflammation
Term
What cytokines are primarily responsible for the development of the DTH response?
Definition
IL-12: drives T cells along Th1 pathway
IFN-Y: activates macrophages/enhances phagocytosis
IL-2: proliferation of T cells
TNF & lymphotoxin: vasodilation, leukocyte attachment
Term
What type of hypersensitivity is useful in diagnosing whether people have been exposed to tuberculosis?
Definition
Type IV hypersensitivity
Term
True or False

DTH is important in granulomatous inflammation
Definition
true
Term
What cells characterize T cell-mediated cytotoxicity?
Definition
CD8+ cells (cytotoxic T cells)
Term
What causes necrosis of cancer cells?
Definition
T-cell mediated cytotoxicitiy
Term
What is an allograft?
Definition
tissue graft between two individuals of same species but with different genotypes
Term
What is the role of histocompatibility molecules?
Definition
bind peptide fragments of foreign proteins for presentation to antigen-specific T cells
Term
What are HLA antigens?
Definition
aka histocompatibility antigens

-antigens on surfaces of nucleated cells
Term
What does the MHC do?
Definition
-encodes 3 classes of molecules
Class I (HLA) found on all tissues
Class II on antigen-presenting cells & B cells
Term
What determines the success of a tissue graft?
Definition
similarity between donor & recipient of the antigens encoded by the major histocompatibility complex
Term
How does Type IV hypersensitivity lead to classic acute rejection?
Definition
-T cells destroy the parenchyma & endothelial cells of the grafted tissue
-T cells damage graft vasculature
Term
Hyperacute rejection occurs when...
Definition
preformed antibodies bind to the graft endothelium causing ischemia & thrombosis
Term
What are the two types of tissue rejection?
Definition
T Cell-Mediated Rejection
Antibody-Mediated Rejection
Term
What is anergy?
Definition
inactivation of lymphocytes
-induced by exposure to antigens under certain conditions
Term
What are primary immunodeficiency diseases?
Definition
genetically determined diseases which affect humoral or cellular immunity, or non specific host mechanisms e.g. complement/phagocytes/NK cells
Term
What type of immunity defect is affected by SCID?
Definition
defects in both humoral and cell-mediated immunity
Term
What are secondary immunodeficiencies?
Definition
immune deficiencies due to malnutrition, cancers, infection, radiation etc.
Term
What causes AIDS?
Definition
infection with the retrovirus HIV
Term
How does HIV lead to AIDS?
Definition
HIV incorporates itself into the cellular DNA, influencing cell function & integrity
Term
True or False

AIDS can lead to cancers & neurologic signs
Definition
true
Term
What are the 3 major routes of HIV transmission?
Definition
Sexual
Parenteral (blood, needles)
Mother-to-Infant
Term
What is the importance of glycoproteins in HIV?
Definition
critical for infection of cells
Term
What is p24?
Definition
a core protein of HIV that is a readily detected antigen
Term
Why is the HIV virus difficult to develop a vaccine for?
Definition
-genome encodes for various proteins, as well as regulates assembly of viral particles
-lots of variability in the genome
Term
Which cells does AIDS show a tropism for?
Definition
CD4+
Term
What is the defining characteristic of AIDS?
Definition
loss of CD4+ cells leading to increased susceptibility to pathogens & cancers
Term
What causes a loss of CD4+ cells in AIDS?
Definition
increased destruction of infected cells
reduces production of CD4 cells
Term
What cells are affected by HIV? How?
Definition
monocytes (reservoirs)
macrophages (reservoirs, transportation)
CD4+
Dendritic cells (transport to lymph nodes)
Term
What are the 3 phases of HIV infection?
Definition
Early Acute: self-limiting, can detect virus-specific antibodies

Middle Chronic: HIV test is positive but few signs of disease, virus replicates in lymph tissues

Crisis phase: severe opportunistic infections, very low CD4+ count, severe viremia
Term
What is an ARC?
Definition
AIDS-related complex

patients are HIV+, symptomatic but dont have any indicator diseases of AIDS such as opportunistic infections, lymphoma
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