PATH3610 Lecture 4: PATH 3610; Unit 04

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3 Feb 2016
Department
Course
Professor
PATH 3610
Unit 4: The Immune System
- Immune response is characterized by its specificity – ability to direct reactivity toward inducing agent
through recognition of antigens
- Also remembering the inducing agent
- Inflammation is nonspecific
- Non-specific defense mechanisms
oSkin and mucous membrane
oPhysical barrier to foreign agents
oCells are routinely sloughed from the surfaces of both preventing organisms from gaining a
foothold
oSkin surface has a slight acidic pH to prevent growth of some organisms
oMucus acts as a protective coating
oCilia helps move foreign particles out of the respiratory tract
oCough mechanisms helps to expel such material more forcefully
- Lysozyme in tears, acid in stomach, digestive enzymes all prevent foreign agents from gaining a
foothold
- Inflammation: example of a nonspecific defense mechanism
- Characteristics of the immune response:
oSpecificity reactivity is directed specifically toward the foreign agent, through recognition of
antigens
oMemory specific antigen is remembered by the body after its initial exposure, recognized
when encountered again
oEnhanced response during second exposure to antigen, amplification
- Antigens: molecules which evoke an immune response when introduced into a host
oLarge molecules, typically protein/polysaccharide
oSmaller molecules (haptens) can become antigenic if complexed with larger carrier molecules
oForeign (extrinsic) antigens include infectious agents (i.e. bacteria, viruses, protozoa, fungi),
transplanted foreign cells, etc.
- Self (or natural tolerance): lack of response to our own body’s antigens
- Antigen enters the body, first processed by antigen-presenting cells, then presented to lymphocytes
oCauses lymphocytes (T and B cells) to proliferate and transform
oCell-mediated immunity (CMI) is a function of T cells
Transform into effector (killer) T cells)
Destroy antigen-bearing cells
Lymphokines are produced, influence interactions between cells
Regulator functions – helper and suppressor T cells enhance and suppress the immune
response
oHumoral immunity is a function of B cells
B cells transform into antibody-producing plasma cells
Antibodies are also known as immunoglobulins
- Immune system produces its own antibodies and T lymphocytes with specific antigen receptors on their
surfaces, under genetic control
4.1 The Cells of the Immune Response
- Lymphocytes: mononuclear cells, large round nucleus that occupies most of the cell
oDerived from stem cells in bone marrow
oLymphocytes which develop in the thymus are called T lymphocytes (T cells)
oLymphocytes which develop independently of the thymus are termed B lymphocytes (B cells)
oThymus and bone marrow are central lymphoid tissues and sites of priming where tolerance
and diversity develop/occur
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oFrom bone marrow/thymus, T and B cells travel to peripheral lymphoid tissues (i.e. lymph
nodes, spleen, tonsils, and gut-associated lymphoid tissue (GALT))
oTravel via blood
- Thymus: a gland, in CT within the chest cavity
- Bursa of fabricius: outgrowth of cloaca in birds, develop B cells
- B and T cells look the same, can only be differentiated by the presence of antigens which act as
immunologic markers
- B cells
oPresence of a cell surface antibody-receptor complex called B-cell receptor complex (BCR)
oAntibodies (Ab) come into contact with their specific antigen (Ag), the Ab/Ag interaction causes
B cells to proliferate and differentiate into two populations:
Plasma cells
Vast majority
Produce and secrete Ab that is specific for the Ag which originally triggered their
differentiation
Distinctive appearance
Memory cells
Small population
Persist for long periods of time
Residual population of B cells that can react to the Ag and invoke a rapid
immune response
Responsible for memory characteristic of immunity
- T cells
oHave a T-cell receptor complex (TCR) on their surfaces
oSpecific to certain Ags
oTCR does not recognize free or circulation Ag, but rather interacts with fragments of Ags that
are expressed on the surface of cells that:
Have phagocytosed and digested a pathogen and are now presenting these Ags on the
surface
Are expressing the
antigen abnormally
oAfter this interaction, T cells
activate, proliferate, and
amplify the immune
response
oMost T cells can be
categorized as either CD4+
or CD8+ cells
CD4 is expressed
on 60% of mature T
cells
CD4+ T cells
are helper T cells
Secrete cytokines
Upregulate the immune response
Can be further subdivided into Th3 and Th2 subtypes
Th3-cell response
oRespond to activation via release of interferon-gamma (IFN- ) which γ
activates macrophages and B cells
oB cells activated will secrete antibody isotypes that mediate phagocytosis
and activate complement
Th2-cell response
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oRespond to activation through release of IL-4, IL-5, and IL-14
oIgE-mediated activation of mast cells and eosinophils, producing a
reaction similar to Type I hypersensitivity response
CD (cluster designation) refers to antigens (proteins) on the surface of T cells
Normal CD4+ : CD8+ ratio is 2:1
CD8 is expressed on ~30% of T cells
Important role as cytotoxic T cells
Kill virus-infected cells and/or tumor cells
- Functions of activated T cells
oCell-mediated immunity (CMI)
Kill any cell which has surface Ag recognized by that T cell
Cytotoxicity: killer T cells cause lysis of such cells by making holes in their cell
membranes
Important function of CD8+ T cells
oHelper roles (regulation of B and T cell activity)
Production of cytokines, soluble protein mediates
Influence function of macrophages and other lymphocytes
Helper T cells (CD4+) help, via secretion of cytokines, the activation of and Ab synthesis
of B cells, and affect cytotoxic T cell function
oDelayed hypersensitivity
T cell-mediated activity
Adverse effects
- Natural killer (NK) cells are another type of lymphocyte
oRecognize microbial glycolipids
oImportance in host defense is not established
oCells of innate immunity
oHave two types of receptors – inhibitory and activating
oInhibitory receptors recognize self-class I MHC molecules, found on all healthy cells
oActivating receptors recognize stressed/infected cells or cells with DNA damage
oNormally, effects of inhibitory receptors dominate over activating receptors preventing
activation of NK cells
- Antigen-presenting cells
oMacrophages: derived from blood monocytes
Concentrated in lymphoid tissues, lungs, liver
Ingest microbes and other Ags
Display peptides for recognition by T lumphocytes
These T cells then activate macrophages to kill the microbes (central reaction of cell-
mediated immunity)
B cells present peptides to helper T cells and receive signals that stimulate Ab
responses to protein Ags
Cytokine IL-1 activates resting T cells and Ag presentation is crucial to stimulation and
differentiation of both T and B cells
Ag-processing role involves phagocytosis and internalization of Ag by the macrophage
Ag is then expressed at the macrophage surface with MHC molecules
Leads to T cell activation and lymphokine release
B cell activation usually involves interaction with macrophages and T cells (some
multivalent antigens can be recognized by B cells directly)
oDendritic cells (DCs)
High levels of class II MHC and T cell costimulatory molecules
Capture and present antigens to T cells
Reside in and under epithelia
Capture entering microbes
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