Infection and Immunity Key Points

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Innate Immunity: Inflammation and Wound Healing
• Two types of human defense mechanisms exist: (1) innate resistance or immunity conferred by natural barriers and (2) the inflammatory response and the adaptive (acquired) immune system.
• Physical and mechanical barriers are the first lines of defense encountered by invading pathogens; these include the skin and mucous membranes.
• Antibacterial peptides in mucous secretions, perspiration, saliva, tears, and other secretions provide a biochemical barrier against invading pathogens in the extracellular space.
• The vascular response in acute inflammation includes vasodilation, increased capillary permeability, and white blood cell adherence to inner vessel walls and their migration through the vessel walls.
• Three plasma protein systems provide a biochemical barrier against invading pathogens in the circulation. These include the complement system, the clotting system, and the kinin system.
• Many different types of cells are involved in the inflammatory process including mast cells, granulocytes (neutrophils, eosinophils, basophils) monocytes or macrophages, natural killer (NK) cells, lymphocytes, and cellular fragments (platelets).
• The inflammatory response is initiated upon tissue injury or when PAMPs are recognized by pattern recognition receptors (PRRs) on cells of the innate immune system.
• Local manifestations of inflammation are the result of the vascular changes associated with the inflammatory process, including vasodilation and increased capillary permeability. The symptoms include redness, heat, swelling, and pain.
• The three primary systemic effects of inflammation are fever, leukocytosis, and an increase in the levels of circulating plasma proteins.
• Chronic inflammation can be a continuation of acute inflammation that lasts 2 weeks or longer. It also can occur as a distinct process without significant preceding acute inflammation.
• Resolution and repair occur in two separate phases: the reconstructive phase, during which the wound begins to heal, and the maturation phase, during which the healed wound is remodeled.
• Dysfunctional wound healing can occur as a result of abnormalities in either the inflammatory response or in the reconstructive phase of resolution and repair.
• Neonates commonly have transiently depressed inflammatory function.
• Infants often have deficiencies in complement and in the number of collectins, making them more susceptible to bacterial infection.
• Older adults are at risk for impaired wound healing, often because of underlying illnesses.
• Diminished immune function may interfere with an older adult’s natural ability to ward off infection.

Adaptive Immunity
• Cells of the innate system most often initiate the adaptive immune response. These cells process and present portions of invading pathogens (e.g., antigens) to lymphocytes in peripheral lymphoid tissue.
• Adaptive immunity can be either active or passive, depending on whether the immune response components originated in the host or came from a donor.
• Antigens are the molecules that can react with components of the adaptive immune system, including antibodies and lymphocyte surface receptors. Immunogens are antigens that can initiate the adaptive immune response. To be immunogenic, an antigen must be the correct type, size, and complexity and present in sufficient quantities. Haptens are small-molecular-weight antigens that are not, themselves, immunogenic.
• The MHC is a cluster of genes found on human chromosome 6. The products of these genes are also called HLA antigens. The MHC genes are highly polymorphic, having many different possible alleles. An individual will carry only two alleles at each locus, one from each parent. The particular combination of alleles a given individual carries defines his or her MHC haplotype.
• During their interactions, cells must communicate with each other through soluble cytokines. In addition to their roles in the innate immune response, cytokines have multiple functions in the adaptive immune response including both positive and negative regulation of B-cell and T cell maturation. In general, the precise combination of cytokines that influence a given cell ultimately determines that cell’s response.
• An individual’s population of T cells and B cells has the collective ability to respond to virtually any antigen.
• Differentiation of B cells and T cells in the primary lymphoid organs results in the expression of several characteristic surface markers, such as CD4 on helper T cells (Th cells), CD8 on cytotoxic T cells, and CD21 and CD40 on B cells.
• Clonal selection is the process during which antigen selects lymphocytes with complementary T-cell receptors (TCRs) or B-cell receptors (BCRs) and induces an immune response with the production of specific antibody or cytotoxic T cells or both.
• For lymphocyte activation, most antigens must be processed and presented by an APC in the context of the appropriate molecule, either MHC class I, MHC class II, or CD1 molecules.
• Most immune responses require Th cells. Precursor Th cells interact with APCs through the TCR/CD4 complex, a variety of adhesion molecules, and cytokines, especially interleukin 1 (IL-1), and develop into either Th1 or Th2 subsets. Th1 cells are responsible for helping activate macrophages and cytotoxic T cells, whereas Th2 cells are responsible for helping activate B cells.
• B cells become activated upon recognition of a particular antigen to proliferate and differentiate into plasma cells that function as factories for the synthesis of large amounts of antibody that are specific for the recognized antigen or into memory B cells.
• T-cell activation results from recognition by the TCR and CD8 of antigen presented by MHC class I. Appropriate intercellular adhesion molecules and cytokines, such as IL-2 from Th1 cells, are also necessary for efficient differentiation. T cells become cytotoxic T cells or memory T cells.
• Whereas antibodies of the systemic immune system function throughout the body, antibodies of the secretory (mucosal) immune system—primarily immunoglobulins of the IgA class—are associated with bodily secretions and function to prevent pathogenic infection on epithelial surfaces.
• The human neonate has a poorly developed immune response, particularly in the production of IgG. Maternal antibody that is actively transported across the placenta protects the fetus and neonate in utero and during the first few postnatal months.
• T-cell activity is deficient in older adults, and a shift in the balance of T-cell subsets is observed. These changes may result in increased susceptibility to infection.

Alterations in Immunity and Inflammation
• Mechanisms of hypersensitivity are classified as type I (IgE-mediated) reactions, type II (tissue-specific) reactions, type III (immune complex–mediated) reactions, and type IV (cell-mediated) reactions.
• Hypersensitivity reactions can be immediate (developing within minutes to a few hours) or delayed (developing within several hours or days).
• Autoimmunity is a breakdown of immunologic homeostasis, the immune system’s tolerance of self-antigens. Central tolerance develops during the embryonic period. Peripheral tolerance is maintained in secondary lymphoid organs by regulatory T lymphocytes or antigen-presenting dendritic cells.
• Autoimmune disease can be caused by the exposure of a previously sequestered antigen, the development of a neoantigen, complications of an infectious disease, the emergence of a forbidden clone of lymphocytes, or ineffective peripheral tolerance.
• Alloimmunity is the immune system’s reaction against antigens on the tissues of other members of the same species.
• Immune deficiencies are either congenital (primary) or acquired (secondary). Whereas genetic defects that disrupt lymphocyte development cause primary immune deficiencies, secondary immune deficiencies are secondary to disease or other physiologic alterations.
• The clinical hallmark of immune deficiency is a propensity to unusual or recurrent severe infections. The type of infection usually reflects the immune system defect.
• Deficiencies in immunity are usually treated by replacement therapy. Deficient antibody production is treated by the replacement of missing immunoglobulins with commercial gamma-globulin preparations. Lymphocyte deficiencies are treated by the replacement of host lymphocytes with transplants of bone marrow, fetal liver, or fetal thymus from a donor.

Infection
• The human body is a hospitable site in which microorganisms can grow and flourish. These microorganisms make up the normal microbiome of the body.
• The process of infection includes colonization, invasion, multiplication, and spread.
• Clinical infectious disease occurs in four distinct stages: (1) incubation period, (2) prodromal state, (3) invasion period, and (4) convalescence.
• Infectious diseases are also classified by their prevalence and spread as endemic, epidemic, and pandemic.
• Classes of infectious microorganisms include bacterial, fungal, parasitic, protozoal, and viral.
• Acquired immunodeficiency syndrome (AIDS) is a viral disease caused by HIV.
• HIV infects and depletes a portion of the immune system (T helper [Th] cells), making individuals susceptible to life-threatening infections and malignancies.
• HIV is a bloodborne pathogen present in body fluids (e.g., blood, vaginal fluid, semen, breast milk) with typical routes of transmission: blood or blood products, intravenous drug abuse, heterosexual and homosexual activity, and maternal-child transmission before or during birth.
• The primary surface receptor on HIV is the envelope glycoprotein gp120, which binds to the CD4 molecule found mostly on the surface of Th cells. Several other important co-receptors have been identified.
• The current treatment for HIV infection is a combination of drugs called antiretroviral therapy (ART).

• The rigorous use of environmental infection control measures, including insect control, modern sanitation facilities, and clean water and food, is effective means of countering infectious microorganisms. Prophylactic or interventive procedures include vaccines and antimicrobial medications.
• With antibiotic-resistant pathogens, a greater emphasis is placed on the development of new vaccines.

Stress and Disease
• The GAS occurs in three stages: (1) alarm stage, (2) stage of resistance or adaptation, and (3) stage of exhaustion. Diseases of adaptation develop if the stage of resistance or adaptation does not restore homeostasis.
• Selye identified three components of physiologic stress: (1) stressor, (2) physiologic or chemical disturbance produced by the stressor, and (3) body’s adaptational response to the stressor.
• Stress has been defined as the state of affairs arising when a person relates to (or interacts or transacts with) situations in a certain way. How a person appraises and reacts to situations is important.
• Real stressors elicit a reactive response that can begin either in the limbic system or in the brain in response to specific sensory information. This information is then relayed to the human paraventricular nucleus (PVN). The PVN stimulates the locus ceruleus and both central and endocrine stress responses.
• The neuroendocrine response to stress consists of sympathetic stimulation of the adrenal medulla to secrete catecholamines (norepinephrine and epinephrine) and stressor-induced stimulation of the hypothalamus to secrete corticotropin-releasing hormone (CRH), which in

turn stimulates the pituitary to secrete adrenocorticotropic hormone (ACTH), which then stimulates the adrenal cortex to secrete steroid hormones, particularly cortisol.
• The nervous, endocrine, and immune systems communicate through the common use of signal molecules and their receptors, which in turn regulate the behavior of cells in each system during stress challenge.
• Stress is a system of interdependent processes that are moderated by the nature, intensity, and duration of the stressor and the coping efficacy of the affected individual, all of which in turn mediate the psychologic and physiologic response to stress.
• With aging, sometimes a set of neurohormonal and immune alterations develop; these changes have been defined recently as stress-age syndrome.

McCance (2019)

Sample Solution

Would it be advisable for us to be permitted to take our very own lives? In numerous societies antiquated and not all that old suicide has been viewed as the best alternative in specific conditions. Cato the Younger submitted suicide instead of live under Caesar. For the Stoics there was nothing essentially corrupt in suicide, which could be normal and the best choice (Long 1986, 206). On the other hand, in the Christian convention, suicide has to a great extent been viewed as unethical, resisting the desire of God, being socially unsafe and restricted to nature (Edwards 2000). This view, to pursue Hume, overlooks the way that by dint suicide being conceivable it isn’t against nature or God (Hume 1986). By the by, being permitted to take our very own lives encroaches on the morals of open strategy in an assortment of ways. Here we will quickly look at the instance of doctor helped suicide (PAS) where a person’s desire to pass on might be supported by the activity of another. Hume viewed suicide as ‘free from each attribution of blame or reprimand’ (Hume 1986, 20) and in reality suicide has not been a wrongdoing in the UK since 1961 (Martin 1997, 451). Helping, abetting, guiding or securing a suicide is anyway a unique statutory wrongdoing, albeit couple of indictments are brought. As of late the issue of PAS has realized the discussion ‘whether and under what conditions people ought to have the capacity to decide the time and way of their demises, and whether they ought to have the capacity to enroll the assistance of doctors’ (Steinbock 2005, 235). The British Medical Association restricts willful extermination (leniency slaughtering) yet acknowledges both legitimately and morally that patients can reject life-drawing out treatment – this that they can submit suicide (BMA 1998). Neglecting to forestall suicide does not establish abetting (Martin 1997, 451) despite the fact that PAS ‘is the same in law to some other individual helping another to submit suicide’ (BMA 1998). In Oregon, be that as it may, PAS, limited to capable people who ask for it, has been authorized (Steinbock 2005, 235, 238). A qualification ought to be kept up among suicide and (leniency) slaughtering, acts in which the specialists vary, however obviously precisely where the line ought to be drawn is a piece of the issue. The moral contentions in help of PAS include enduring and independence (Steinbock 2005, 235-6). The principal affirmation is that is merciless to draw out the life of a patient who is in torment that can’t be medicinally controlled; the second, in the expressions of Dr Linda Ganzini dependent on her investigation in Oregon, includes the possibility that ‘being in charge and not subject to other individuals is the most essential thing for them in their diminishing days’ (cited in Steinbock 2005, 235). The coherent result of these contentions is that, if PAS can be supported on the grounds of torment or self-governance, for what reason would it be a good idea for it to be limited to skillful people or the critically ill? Surely the judge in Compassion in passing on v State of Washington (1995) expressed that ‘if at the core of the freedom secured by the Fourteenth Amendment is this uncurtailable capacity to accept and follow up on one’s most profound convictions about existence, the privilege to suicide and the privilege to help with suicide are the right of no less than each rational grown-up. The endeavor to limit such rights to the critically ill is deceptive’ (Steinbock 2005, 236). As noted above, religious dissatisfaction with suicide has turned out to be less pertinent an as referee of morals and approach. In fair social orders that may best be depicted as mainstream with a Christian legacy, the perspectives of religious gatherings ought not confine the freedom of people in the public arena (Steinbock 2005, 236). Others contend that the job of the doctor is to mend and help and not to hurt, however supporters of PAS would state that passing isn’t constantly destructive and helped suicide is an assistance. Undoubtedly, in a nation where PAS isn’t lawful individuals who wish to bite the dust without condemning the individuals who aid their suicide might be driven abroad, as on account of Reginald Crew who was kicking the bucket of engine neurone sickness and made a trip to Switzerland for AS, biting the dust in January 2002 (English et al. 2003, 119). This may cause more damage through the worries of disengagement and stress than enabling the PAS to happen. The two most genuine concerns are that PAS would be mishandled and would prompt negative changes in the public arena. This could occur from numerous points of view through defenseless gatherings, for example, poor people, the elderly and so on, being constrained into picking PAS (Steinbock 2005, 237). The BMA underscores a worry for the message that would be given to society about the estimation of specific gatherings of individuals (BMA 1998). This is a piece of a more extensive concern additionally communicated in a Canadian Senate enquiry of 1995 (BMA 1998) which focuses to a strategy of suicide anticipation among some defenseless gatherings that would be rendered odd by looking to ease suicide among the debilitated. Notwithstanding, the introduction is somewhat deceitful, since there is a distinction in the explanation behind potential suicide that must be examined. For instance, looking to counteract suicide among the adolescent may include projects of social consideration or expanding life prospects, and this style of arrangement isn’t appropriate on account of the individuals who may look for PAS. In Oregon in any event, it appears that feelings of dread about PAS have not emerged, and one specialist presumes that the generally low utilization of PAS is characteristic of it being excessively prohibitive (Steinbock 2005, 238). Clients of PAS, as opposed to being poor people and socially defenseless as anticipated, would in general be working class and taught, with more youthful patients bound to pick it than the elderly, and most were selected in hospice care. Issues about PAS and killing should be cleared up and contended independently. With regards to this issue at any rate, the topic of whether suicide ought to be permitted is the wrong one to inquire. A beginning stage is to ask how skilled people can be permitted to satisfy their desires as to life and demise issues without imperiling other individuals, regardless of whether specialists or friends and family and whether widely inclusive enactment is possible.

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